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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1980-12-01 to 1980-12-29
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Inadequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
10 rabbits (5 male, 5 female) dermally exposed to repeat doses of 500 mg/kg bw/d for 5 consecutive d/wk for 2 wks
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): C9 aldehyde; C-192
- Substance type: Colourless liquid
- Physical state: Liquid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: Room temperature under nitrogen blanket

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania, United States
- Age at study initiation: Young adults
- Weight at study initiation: Males 2.1 to 3.2 kg; females 2.3 to 3.2 kg
- Fasting period before study:
- Housing: Individually in suspended stainless steel cages
- Diet: Ad libitum rabbit chow
- Water: Ad libitum mains water
- Acclimation period: 21 d

ENVIRONMENTAL CONDITIONS
- Temperature: 60 to 70 °F (i.e. (16 to 21 °C)
- Humidity (%): Monitored daily
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Vehicle:
other: Mineral oil
Details on exposure:
TEST SITE
- Area of exposure: Dermal and lateral skin, approx. 10 % of body area.
- Time intervals for shavings or clipplings: Before first exposure, as necessary during test period.
- Abrasion of the skin of animals prior to the 1st, 6th and 8th doses unless otherwise integrity of the skin had already been compromised due to a response to the test material.
- No covering was applied.
- Test material in vehicle was spread evenly over the exposure site with a glass rod.

TEST MATERIAL IN VEHICLE
- Dosage applied: 500 mg/kg bw/d of test material
- Concentration: 25 % in vehicle solution
- Doses adjusted weekly on the basis of most recent body weight data.

RESTRAINERS FOR PREVENTING INGESTION
- Elizabethan collars.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 wks
Frequency of treatment:
Daily for 5 d/wk
Doses / concentrations
Remarks:
Doses / Concentrations:
500 mg/kg bw
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5 male, 5 female per single dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale:
- Rationale for animal assignment: Random

Examinations

Sacrifice and pathology:
SACRIFICE
- 2 wks: 6 animals (3 with abraded skin, 3 with intact skin, regardless of sex)
- 4 wks: All survivors
- Method: Exsanguination under sodium pentobarbital anaesthesia.

HISTOPATHOLOGY
- Tissues preserved in 10 % neutral buffered formalin: Adrenals (2), brain (2 sections), eyes, gonads, heart, intestine (colon, duodenum, ileum), kidneys (2), liver (2), lungs (2), lymph node (mesenteric), mammary gland, pancreas, pituitary, salivary gland, skeletal muscle, skin (both treated and untreated sections), spinal chord (cervical), spleen, stomach, thyroid, urinary bladder, uterus/prostate, gross lesions, tissue masses.
- Slides prepared from tissues, stained with haematoxylin and eosin, and examined microscopically: Brain (2 sections), heart, skin (both treated and untreated sections), kidneys (2), liver (2), lungs (2).
Statistics:
None.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
- No mortality.
- Nasal discharge and vocalisation when handled were noted occasionally.
- No unusual signs other than the dermal observations listed below were seen during the recovery period.

BODY WEIGHT AND WEIGHT GAIN
- Most animals exhibited slight weight loss (0.1 to 0.6 kg) after 1 and/or 2 weeks of study.
- Animals held for a recovery period gained weight during this interval.

FOOD CONSUMPTION
- Several animals exhibited decreased food consumption, primarily during the 2nd and 3rd weeks.

GROSS PATHOLOGY
- Morphological abnormalities of the treated skin were observed more frequently in rabbits from the test group than in the control group.
- Discolourations of gastric mucosa were observed in several of the treated animals [NB: it is not clear to what extent this statement applies to the test material of interest versus the other test materials tested concurrently].
- Other morphological findings observed grossly occurred sporadically in the treated and/or control animals. They did not appear to be related to the administration of the test compounds [NB: it is not clear to what extent this statement applies to the test material of interest versus the other test materials tested concurrently].

HISTOPATHOLOGY: NON-NEOPLASTIC
- Epidemial necrosis was present in the application sites of animals from the treatment group. This was generally less severe and more localised than groups concurrently treated with two other substances and was accompanied by epidermal hyperplasia and hyperkeratosis. Diffuse and perifollicular dermal inflamation was also common.
- The skin application sites in all surviving animals appeared healed by 2 wks post-treatment (scheduled recovery period). In all cases the sites were re-epitheliased and continuous; they also revealed mild to moderate epidemial hyperplasia and hyperkeratosis as well as normal follicular structure and population.

Effect levels

Basis for effect level:
other: No NOAEL identified as effects seen at single dose level of 500 mg/kg bw/d.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The test substance was assessed for repeat dose dermal toxicity in rabbits. No NOAEL was identified as effects were seen at the single dose level of 500 mg/kg bw/d.