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J. Anim. Physiol. a. Anim. Nutr. 77 (1997), 61-65 Eingang des Ms.: 5. 11.

1996
0 1997 Blackwell Wissenschafts-Verlag, Berlin
ISSN 0931-2439

‘3. Grisolia’ Research Unit and 2Preventive Medicine Department, Hospitals Vall
d’Hebron, Passeig Vall d’Hebron, Barcelona, Spain

Body surface area in Sprague-Dawley rats


J. ROSSELL~’
By M. FARRIOL’, and S. SCHWARTZ‘

Introduction

Rats are the most extensively used animal species in the experimental laboratory and have
been employed in a large number of research fields. As they are relatively inexpensive,
Sprague-Dawley and Wistar rats are the most commonly-used in scientific studies and are
the best animal model for multiple studies. These studies include work concerning burns
(ZAPKrA-SIRvEm et al. 1986; FARRIOL et a]. 1994) pharmaceutical studies (REILLY and WORK-
MAN 1993; GRAY et al. 1991), investigations in nutrition ( D E M I C H E Lal.E 1989)
~ ~ and ageing
(MCCARTER and PALMER 1992) for which the measurement of the body surface area of these
animals is essential. A recent work by SMITHet al. (1995), showed that models for predicting
dose measure of drugs gave more correct estimations when the dose administered was scaled
to body surface area.
Using mathematical approaches, different calculations have been devised based o n body
weight to estimate the body surface area of experimental rats. Attempts have been made to
improve the precision of these estimations by adding other body parameters to the empirical
formulas.
Calculations to determine the body surface area in Wistar rats have been available for
many years and have been reviewed (SANROMAN et al. 1985), and recently data from cotton
rats have been reported (OHWADA and KATAHIRA 1993). However, studies with Sprague-
Dawley rats have not clearly defined this question. The growth curve is different in these
rat species and the measurements described for one species are not necessarily applicable to
others.
The aim of the study was to measure the body surface area of Sprague-Dawley rats and
to compare the results with those obtained using four different mathematical formulas,
dcscribed by four authors, t o estimate this parameter.

Material and methods

Seventy male Sprague Dawley rats weighing 79-674 g were studied. The animals were killed
by an overdose of ether anaesthesia. The weight, abdominal length mouth-penis, abdominal
length mouth-tail at the juncture or root, tail length, tail perimeter (at juncture) and body
surface area (BSA) were measured for each of them.
In order to determine the gold standard (GS) surface area, the skin of the animals was
dissected completely and measured by the same technical assistant throughout the process.
The extremities were severed at the tarso and carpo, pressed on an ink pad and imprinted
on paper. The dissected skin was immediately placed on a sheet of filter paper, with the
interior side down, and pressed vertically to avoid stretching.
The skin form was outlined and photocopied on identical sheets of paper. The total
surface image was cut out and weighed. The values obtained were interpolated on a curve

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62 M. Farriol, J. Rossello and S. Scbwartz

2
I. BSA=KxWx-
3

2. BSA=KxW

0.34
3. BSA = 6.67 x W0.7x

2.54 x W0.7x L
4. BSA=
fi
FLg. 1. Formulas used in this study. K=constant; W = weight; L = length mouth-tail

madc with the same material. The resulting measured surface area values werc considered
t o bc the GS.
T h e GS of each rat was compared with the BSA obtained using thc four mathematical
equations (SANROMANct al. 1985) attributcd to MEEH(I), RUBNEK(2), VALLOIS(3) and
SAN ROMAN(4) (Fig. 1).
A n intra-class correlation coefficicnt ANOVA (SPSS statistics softwarc) was applied to
detcrniinc the degree of concordance betwecn the measured body surfacc area and that
calculatcd by the four formulas.
In addition, to detcrmine whethcr body mcasurcments other than those used in the
formulas could be good indicators of BSA, the Pcarson coefficicnt of correlation was
pcrforincd betwcen thc weight of the rats and four body parameters (tail, mouth-tail,
mouth-penis, tail perimeter).

Results

T h c GS surfacc area obtained in the 70 rats studicd ranged from 177 to 733 cm2 (Table 1 ) .
T h c correlations (r) bctween weight and the body lengths described above were: weighthail,
r = 0.943; wcight/mouth-tail, r = 0.981; weight/mouth-penis, r = 0.967; weighdtail-
pcrimctcr, r = 0.895. Thc intra-class corrclation coefficient between the GS and the four

Table 1. Number of animals in each range of measured


body surface

Total body surface (cm’) Number of animals

100-200 2
200-300 17
300-400 6
400-500 13
500-600 9
600-700 18
700-800 5
Body surface in Sprague-Dawley rats 63

formulas showed excellent reproducibility: formula 1 (MEEH), r = 0.837; formula 2


(RUBNER),r = 0.941; formula 3 (VALLOIS),r = 0.993; and formula 4 (SANROMAN),r = 0.961.
Statistically significant differences (p < 0.05) were found between the GS and formula 1,
formula 2, and formula 4. The intra-class correlation coefficient obtained using VALLOIS’
formula was closest to perfect reproducibility (r = I), with no significant differences.
T o evaluate the degree to which the various estimated values approached the GS, the
mcan of the deviation in percentages (absolute value) was calculated. It was confirmed that
for the entire sample, the VALLOISformula offered the smallest mcan deviation: 3.65%, as
compared to formula 1 (22.25%), formula 2 (12.18%) and formula 4 (9.4%).
In light of these findings, a further study that compared, animal by animal, the BSA data
obtained with the VALLOISformula and the GS was performed. The body surface area
obtained with the formula was subtracted from the measured body surface results. There
were positive differences (lower results) in 28/44 rats, and negative differences (higher
results) in 21/26 rats. When the animals were evaluated according to positive or negative
differences, we found that the point of inflection of these differences was at a body weight
of 300 g.
The GS and data from the VALLOISformula were classified into two groups according
to the inflection point (GSl and V1: < 300g; GS2 and V2 > 300g). The mean values of
the groups were: GSl = 260.6 61.5; GS2 = 585.9 f 95.1; V1 = 253.4 & 63.3 and V2 =
597.2 f 94.6. No statistically significant differences between the GS and data from VALLOIS’
formula were found with this new classification. At the cut-off point of 300 g, the means of
the differences were, once again, less for the VALLOISformula (3.96% for animals over
300 g and 5.09% for those under).
Thus, in the small animals (under 300 g) the body surface was underestimated and in the
large animals (over 300g) it was overestimated with VALLOIS’ calculation, by a mean of
20 cm‘. When the results from the formula were adjusted according to body weight of
the animal by adding o r subtracting this figure, the intra-class coefficient of correlation
improved by five-thousandths of a point, from 0.993 to 0.998.

Discussion

The effort to define a simple method for determining body surface area in animals and
humans has a long history. In 1879, a formula was devised by MEEH to estimate this
parameter in rats used for experimentation. In this calculation, animal weight was the only
measurable factor taken into account to estimate surface area, and this was added t o a
constant depending on each animal species. Since body weight is a variable that depends on
sex and age, this method did not produce a precise estimation for the different species of
animals. Over the years, attempts have been made to improve on this initial approach and
to optimize the system of calculation.
It is known that adult land mammals exhibit geometric similarity over a substantial weight
range and relatively constant partitioning of body weight and surface area among the body
segments (PROTHERO 1992). The shape of animals has been traditionally modelled as a series
of cylindrical sections. If the animal has a form close to a regular geometric shape, as is the
case of the snake, it is very easy to estimate surface area by simple arithmetic, without taking
the weight into account.
However, when the animal has a more irregular form, other empirical considerations
must be included to arrive at an accurate estimation. Thus, investigators attempting to find
a more precise estimation of body surface area in animals have introduced other measure-
ments in their formulas.
It is clear that the body segments comprising the longitudinal axis determine a large
proportion of total body weight. A recently-published study (PROTI-IERO 1992) has shown
that the head-trunk body segment constitutes some 70% of the body weight for a given
64 M . Farriol, J . Rossello’ and S. Schwartz

species. W o r k i n g w i t h t h e dog, VALLOIS i n t r o d u c e d ‘abdominal length’ (mouth-tail) in his


calculations. T h i s parameter, directly related t o t h e f o r m of t h e animal, proved t o b e a good
choice.
T h e weight of t h e animal, w h i c h c o r r e s p o n d s t o its age, is t h e m o s t reliable indicator of
n o r m a l g r o w t h a n d a satisfactory state of health. I t has been described (GOLDSPINK and
KELLY1984) i n rats t h a t t h e body weight increased approximately 3550-fold from t h e fetal
age of 14 d a y s to senility (105 weeks). After 6 m o n t h s , thc weight of t h e rats reaches a
plateau a n d a change in t h e g r o w t h c u r v e is p r o d u c e d .
T h e c o m p a r i s o n of t h e measured surface of t h e animals studied a n d t h e d a t a obtained
w i t h t h e VALLOIS f o r m u l a s h o w s that this calculation is a very accurate s y s t e m f o r estimating
t h e surface area of Sprague-Dawly rats. T h e slight e r r o r s t h a t arose in t h e measurements of
animals a t both extremes of the weight range studied do n o t imply a serious flaw in t h e
system. T h e fact of measuring t h e length of t h e animal, although a simple act, w a s translated
i n t o great precision i n t h e formula.

Summary
A study was designed to measure the body surface area of Spraguc-Dawley rats and to compare thc
results with those obtained using the mathematical formulas described by four authors to estimate this
parameter. The animals were killed by an overdose of ether anaesthesia. To determine the gold standard
body surface area, the skin of the animals was dissected completely and measured. The gold standard
was compared with the body surface area obtained in the same rats using the mathematical equations
proposed by MEEI-I,RUHNEK, VALLOIS and SAN ROMAN.Analysis of variance showed statistically
significant differences (p < 0.05) in body surface area results between the gold standard and MEEH’S,
RUBNIX’S,and SAN ROMAN’Sequations. However, no significant differences were found with
VALLOIS’S formula, indicating that results with this calculation were similar to the measured body

*
surface. Further statistical analysis showed that in the small animals the body surface area was under-
cstimatcd and in thc large animals it was ovcrestimated by a mcan of 20cm’ using the Vallois formula.

Zusammenfassung
Die Messung der Korperoberjlache bei Sprague-Dawley Ratten
In der vorliegenden Untcrsuchung wurde die Korperobcrflache von Sprague-Dawley Ratten gemessen
und mit Resultaten aus mathematischcn Formeln von vier verschiedenen Autoren verglichen. Die Tiere
wurdcn durch eine Uberdosis von Ether getotet, um dann mit Hilfe des Umrisses der Haut die
Korpcroberflachc zu messen. Die Ergebnisse aus der Hautoberflachen-Messung wurde mit den Glei-
chungen von MEEH,RUBNER,VALLOISund SANROMANverglichen. Die Varianzanalyse zeigt deutli-
chc statistische Unterschiede (p < 0,05) zwischen dem ermittelten Wert und den mathematischen
Ableitungcn bzw. Gleichungen von MEEH,RUBNERund SANROMAN.Es wurden keine statistischen
Unterschiede zwischen den vorliegenden Messungen und der Formel von VALLOIS gefunden. Das
zeigt, da8 dic Ergebnisse dieser Berechnung in ihrcr Genauigkeit ubereinstimmen. Zusatzliche Analysen
zeigcn, da8 die Anwcndung der VAL1201s’schenFormel die Korperoberflache kleiner Tierc unterschatzt
und die gro8er Tierc um einen durchschnittlichen Wert von 20 cmz uberschatzt.

References

DEMICHELI?, S.J.; KAKLSTAD, D.; BKISTIAN, B. R.; ISTFAN,N.; BAIMYAN, V. G.; BLACKBURN, G . L.,
1989: Am. J. Clin. Nutr. 50, 1295.
FARKIOI.,M.; SCHWAKIZ,S.; ROSSELI-0,J.; GALAKD, R.; CATALAN, R.; HUGUI:T,P., 1994: Burns 20,
496.
GOLDSPINK, D. F.; KEILY‘, F. J., 1984: Biochem. J. 217, 507.
GRAY,J. H.; H E N R Y D. , A,; FORBES,M.; GERMAN,E.; ROBERTS,F. J.; SNELIANG, C. F. T., 1991:
Burns 17, 37.
MCCARTEK, R. 1.; P A L M E R , J., 1992: Am. J. Physiol. Endocrinol. Met. 263, E448.
Body Jutface in Sprague-Dawley rats 65

OHWADA,K.; KATAHIRA, K., 1993: Jik. Dob. 42, 635.


PROTHERO,J., 1992: Am. J. Physio. 262, 492.
REILLY,J. J.; WORKMAN,P., 1993: Can. Chem. Pharmacol. 32, 411.
SANROMAN,F.; SANCHEZ-VALVERDE, M. A,; BONAFONTE,J. I.; SANCHEZ-VALVEKDE,B.. 1985: Sci.
Tec. Anim. Lab. 10, 181.
SMITH,A. E.; GRAY,G. M.; EVANS,J. S., 1995: Reg. Toxicol .Pharmacol. 21, 339.
ZAPATA-SIRVENT, R. L.; HANSBROUGH, J. F.; BENDER,E. M.; BARTLE,E. 1.; MANSOUK,M. A,;
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Authors’ address: M. FAKRIOL and S. SCHWARTZ, ‘S. Grisolia’ Research Unit, Hospitals Val1 d’Hebron,
Passeig Val1 d’Hebron 119-129, Barcelona (08035), and J. R O S S E L L Department
~,
of Preventive Medicine, Hospitals Val1 d’Hebron, Passeig Val1 d’Hebron 1 19-129,
Barcelona (08035), Spain.

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