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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
28 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Stoddard solvent
EC Number:
232-489-3
EC Name:
Stoddard solvent
Cas Number:
8052-41-3
Molecular formula:
C10H22
IUPAC Name:
stoddard solvent
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- 10 of each gender per test group and control group

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on exposure:
Stoddard Solvent CAS# 8052-41-3) was evaluated for toxicity in New Zealand White (NZW) rabbits when administered to the skin 3 times per week over the course of 4 weeks. Stoddard Solvent was applied to the clipped, intact skin of groups of male and female rabbits (5/sex/group) at dose levels of 0, 200, 1000, or 2000 mg/kg. Immediately following application, the sites were covered with surgical gauze, wrapped with polyethylene material and taped for 6 hours. At the end of 6 hours, the occlusive wrapping was removed and any excess material gently wiped off. One female from the high dose group (group 4) was sacrificed in a moribund condition on Day 14, after showing decreased feed intake on Days 12 through 14 and marked weight loss on Day 14. Microscopic examination revealed mucoid enteritis as a probable cause of morbidity and was considered incidental to treatment. Weight gains of males from groups 2 and 3 (200 and 1000 mg/kg) were comparable to those of control males.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks.
Frequency of treatment:
Once per day, 3 times per week (12 total applications)
Doses / concentrationsopen allclose all
Dose / conc.:
200 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
Dose / conc.:
2 000 mg/kg bw/day
No. of animals per sex per dose:
groups of male and female rabbits (5/sex/group)
Control animals:
yes, concurrent no treatment
Details on study design:
The shaved intact skin (15 × 20 cm) of groups of 10 New Zealand White rabbits was exposed to doses of 200, 1000, and 2000 mg/kg of white spirit (Stoddard solvent).
Exposure was carried out usining occlusion bandage for a duration of 6 h and was given 3 times weekly for 4 weeks.

Examinations

Observations and examinations performed and frequency:
The animals were observed for signs of overt toxicity, dermal irritation, effects on body weight and consumption, haematology and serum chemistry parameters.
Sacrifice and pathology:
Complete necropsies were performed on all animals.
Other examinations:
Selected organs were weighed and a microscopic examination was conducted on selected tissues from all animals at the scheduled necropsy.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
At 2000 mg/kg, female rabbits developed liver lesions characterized as white streaks or foci with granular surface
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
Dermal irritation was scored as being severe in group 4 males and females and group 3 males and moderate in group 3 females and group 2 animals (males and females).
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
At the highest dose level, there was a significant reduction in weight gain in both sexes, whereas only the female body weight gain was reduced at 1000 mg/kg.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Mean food consumption (evaluated as g/animal/day) was slightly but consistently decreased in the high dose group (males) during the first two thirds of the study period, and this was attributed to the test article.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
No information provided
Ophthalmological findings:
not specified
Description (incidence and severity):
No test related ophthalmic lesions were present at the week 12 opthalmologic examinations.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Changes in haematological parameters noted at 2000 mg/kg were judged not to be treatment- related.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
In the serum chemistry parameters albumin means were decreased and globulin means were increased (resulting in decreased A/G ratios). Again this was attributed to the acute dermal inflammation that was observed.
Urinalysis findings:
not specified
Description (incidence and severity):
No information provided
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Group 4 females (2000 mg/kg) showed a negative weight gain and significantly lower terminal body weights relative to controls.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No significant changes reported (except for the dermal application sites for all the dose groups)
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
No significant changes reported (except for the dermal application sites for all the dose groups)

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
other: on the basis of a l reduced absolute mean liver weight and increased relative mean kidney weight (left kidney).

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Microscopic examination revealed mucoid enteritis as a probable cause of morbidity and was considered incidental to treatment. Weight gains of males from groups 2 and 3 (200 and 1000 mg/kg) were comparable to those of control males.

Males from group 4 (2000 mg/kg) showed significantly lower weight gains and, subsequently, significantly lower body weights than controls at terminal sacrifice. Females from group 2 had body weight gains comparable to controls, while group 3 females had significantly lower weight gains and terminal body weights than control females.

Group 4 females (2000 mg/kg) showed a negative weight gain and significantly lower terminal body weights relative to controls.

Dermal irritation was scored as being severe in group 4 males and females and group 3 males and moderate in group 3 females and group 2 animals (males and females).

 

 Group 4 (2000 mg/kg) males had significantly reduced absolute mean liver weight and increased relative mean kidney weight (left kidney). Females from groups 4 and 3 showed a significant increase in relative cerebrum weight over controls.

 

The majority of lesions noted upon gross examination at necropsy were seen in the skin and were associated with dermal irritation. Females in the high dose group were seen to have white streaks or foci on the livers of 2 animals, while a third exhibited a granular surface on the liver. Other gross lesions observed in treated animals were few, uniformly small, and occurred with the same frequency as in controls. Microscopic examination of treated animals revealed lesions in the skin at the application site including thickening and down-growth of the epidermis, hyperkeratosis, and dermal fibrosis. The incidence and severity of the observed lesions were significantly greater in high dose animals compared to controls and animals in the lower dose groups. There were a small number of lesions noted from other tissues (heart, trachea, pancreas, testes, and spleen) but these were considered unrelated to treatment.

Applicant's summary and conclusion

Conclusions:
The NOAEL for this study was determined to be 2000 mg/kg.
Executive summary:

The shaved intact skin (15 × 20 cm) of groups of 10 New Zealand White rabbits was exposed to doses of 200, 1000, and 2000 mg/kg of white spirit (Stoddard solvent). Exposure was carried out using occlusion bandage for a duration of 6 h and was given 3 times weekly for 4 weeks. At the highest dose level, there was a significant  reduction in weight gain in both sexes, whereas only the female body  weight gain was reduced at 1000 mg/kg. Changes in haematological parameters noted at 2000 mg/kg were judged not to be treatment-related. At 2000 mg/kg, female rabbits developed liver lesions characterized as white streaks or foci with granular surface

.