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Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
other: published data
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
C12 LAS; Linear Alkylbenzene Sulfonate (LAS)) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.

Data source

Reference
Reference Type:
publication
Title:
Effect of dermal exposure to LAS detergent and HCH pesticide in guinea pigs: biochemical and histopathologic changes in liver and kidney
Author:
Mathur AK, Narang S, Gupta BN, Singh A, Singh S and Shanker R
Year:
1992
Bibliographic source:
J. Toxicol.-Cut. Ocular Toxicol., 11(1), 3-13

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
3 groups were treated on the clipped area with LAS for 30 days
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
C12-LAS
IUPAC Name:
C12-LAS
Details on test material:
LAS, activity: 99.9%

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Forty-eight guinea pig weighing approximately 250g each were obtained from the animal house colony of the Industrial Toxicology Research Center- Housing: The animals were kept in separate cages to keep them from licking the applied chemical.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on exposure:
-Skin (2x2cm) from the back of each animals was clipped free of fur using an Oster electric clipper.
- Control group: acetone (0.5mL) was applied to the clipped skin.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
60mg/kg bw/day in distilled water
Basis:
nominal per unit body weight
No. of animals per sex per dose:
48 guinea pigs organized into four groups
Control animals:
yes
Details on study design:
- Control group: acetone (0.5mL) was applied to the clipped skin.- Skin (2x2cm) from the back of each animals was clipped free of fur using an Oster electric clipper.
- After autopsy, a portion of liver and kidney was cut and transferred immediately to cold Petri dishes. These tissues were then homogenized in ice cold 0.25M sucrose solution (10% w/v) for biochemical studies and in 0.15 M KCl for lipid peroxidation using a Potter Elvehjem type homogenizer.

Examinations

Observations and examinations performed and frequency:
1)Enzyme assays: determinded in liver and kidney homogenates.- β-glucuronidase: assay system: contained acetate buffer (0.6 mL, 0.2 mol/L, pH 4.9), phenolphthalein glucuronic acid solution 0.2 mL (0.03 mol/L, pH 4.5), water 0.2 mL, and homogenate 0.2 mL. The mixture was incubated at 56 deg C for 1 hr with 5.0 mL 2-amino-2-2 methylpropanol buffer (0.1 mol/L, pH 11) according to the method of Fishman. The absorbance was read at 550nm against water.- Gamma glutamyl transpeptidase: assay system: contained 0.5 mL 51 μmol L-v-glutamyl-p-nitroanilide, 0.02 mL homogenate, 2.0 mL 1.7 N acetic acid, 1.0 mL 0.1% sodium nitrate, 1.0 mL 1% amonium sulfamate, and 1.0 mL 55 mg/100 mL naphthylene diamine according to the method of Naftalin. The absorbance was read at 550 nm and the activity expressed as units/mg protein.- 5-nucleotidase: assay system: contained 4.8 mL AMP (250 μmole, pH 7.5), glycerophosphate 4.8 mL 160 μmoles pH 7.5, homogenate 0.1 mL. The mixture was incubated at 37 deg C for 2.5 hr and the reaction was stopped by the addition of 30% trichloroacetic acid (TCA), according to the method of Dixon and Purdom. The contents were centrifuged, the concentration of Pi was determined, and the activity was expressed as units/mg protein.- Sorbitol dehydrogenase: reaction mixture: contained 0.2 mg NADH, 2.0 mL Tris buffer (0.1 mL/L pH 7.5), 0.05ml homogenate, 0.5 mL fructose 72 g/100 mL, according to the method of Asada and Galambos. The absorbance was read at 340 nm against potassium dichromate (3 g/100 mL). The values are expressed as μmole NADH oxidized/min/mg protein.

2) Lipid peroxidation, glutathione, and protein determinationsLipid peroxidation was determined by the thiobarbituric acid reaction spectrophotometrically, according to the method of Ohkawa, and expressed as μmole malonaldehyde formed/hr/mg protein.- Glutathione: determined by the DTNB method of Jollow.The protein content of the homogenate was estimated by the Folin-phenol reagent method of Lowry after being precipitated with TCA.

3) Histopathologic Remaing parts of the liver and kidney were fixed in 10% buffered formalin and then subsequently processed for the preparation of histologic sections using routine microtomy and staining procedures.
Sacrifice and pathology:
After 30 days of treatment, the animals were sacrificed

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
- Liver enzymes: The activity of GGT, SDH was significantly increased.
- Kidney enzymes: The activity of β-glucuronidase was increased for a period of 30 days.
- Lipid peroxidation(LPO) and GSH contents of liver and kidney: LPO was increased in the liver and there were no effects on GSH contents.
- Histologic finding- Liver: Prominent fatty changes involving large areas of hepatic lobule and accompanied by by dilation of sinusoids were observed result from 30 days of exposure to LAS.
- Histologic finding -Kidney: Injuries manifest mostly in the tubular region of nephron, predominantly confined to proximal and distal convoluted tubules were observed result from 30 days exposure to LAS.

Effect levels

Dose descriptor:
LOAEL
Effect level:
60 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: The LOAEL is 60 mg/kg bw/day based on biochemical and histologic finding.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Biochemical findings were observed with increasing activities of β-glucuronidase, 5ND, GGT and LPO. And the extensive fatty changes were found in hepatic lobules and tubular lesions were found in the kidney. Therefore LAS produce damage to hepatic and renal tissue after dermal exposure.
The LOAEL is 60 mg/kg bw/day based on biochemical and Histologic finding.