Butanenitrile, 2-amino-2,3-dimethyl-

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, and is acceptable for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Robust Summary for Aminoalkylnitrile Category

Author:

US EPA HPVIS

Year:

2006

Bibliographic source:

Doc ID 201-16274

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Principles of method if other than guideline:

A 28-day repeated dermal neurotoxicity study with 94.2% 2-amino-2,3-dimethylbutanenitrile was conducted to assess its potential to cause systemic toxicity and adverse effects on the nervous system. Test substance was administered dermally to rats (5/sex/group), at concentrations of 0, 3, 10, and 30 mg/kg (0, 3.578, 11.932, and 35.775 ml/kg) for 28 days (5 days/week, 6 hrs/day for 4 weeks). Test material was applied by gentle inunction
over the clipped area of unabraded skin. Dosages adjusted at 3-day intervals to accommodate body weight changes. The treated area was covered with an impervious patch. After 6 hrs, the patch was removed and the treated area thoroughly cleansed. Detailed observations, body
weights, and food consumption values were recorded at 3-day intervals.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-2,3-dimethylbutanenitrile

Cas Number:

13893-53-3

Molecular formula:

C6H12N2

IUPAC Name:

2-amino-2,3-dimethylbutanenitrile

Details on test material:

Purity: 94.2%

Test animals

Species:

rat

Strain:

other: Charles-River CD (Sprague-Dawley derived)

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on exposure:

Test substance was administered dermally to rats (5/sex/group), at concentrations of 0, 3, 10, and 30 mg/kg (0, 3.578, 11.932, and 35.775 µl/kg) for 28 days (5 days/week, 6 hrs/day for 4 weeks). Test material was applied by gentle inunction over the clipped area of unabraded skin. Dosages adjusted at 3-day intervals to accommodate body weight changes. The treated area was covered w/ an impervious patch. After 6 hrs, the patch was removed and the treated area thoroughly cleansed.

Duration of treatment / exposure:

6 h a day/ 4 week exposure

Frequency of treatment:

5 days a week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 3, 10, and 30 mg/kg (0, 3.578, 11.932, and 35.775 µl/kg)
Basis:

No. of animals per sex per dose:

5

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Detailed observations, body weights, and food consumption values were recorded at 3-day intervals.

Sacrifice and pathology:

All animals were perfused with 10% buffered neutral formalin solution prior to necropsy. The weights of the liver, kidney, heart, thyroid glands, brain, and gonads were recorded.

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

3 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: for local effects (skin irritation)

2

Dose descriptor:

NOAEL

Effect level:

>= 30 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: for systemic effects with special focus on neurotoxicity

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

All rats survived the experimental period. There were no overt signs of toxicity observed at any treatment level; body weight gain, diet consumption, hematology and clinical chemistry values were comparable across all groups.

The weights of the liver, kidney, heart, thyroid glands, brain, and gonads were recorded. A statistically significant increase in absolute thyroid weights was observed in male rats at all treatment levels. Thyroid weights for females were somewhat increased though not significantly. Relative thyroid weights were also somewhat increased at all levels in both sexes with a significant increase in males at the 3 mg/kg level.

Subsequent histopathology failed to find any pathologic change that would account for this finding. No other significant organ weight changes were observed at any treatment level. No test article related gross or microscopic lesions were observed in the tissues samples from the adrenal gland, bone marrow, brain, eye and optic nerve, heart, liver, kidneys, lung, ovary, skeletal muscle, sciatic nerve, skin, spinal cord, testes, thyroid glands, and uterus. There were no overt signs of neurotoxicity (no lacrimation, no salivation, no tremors, no convulsions, no increased urination, no diarrhea, no piloerection) at any treatment level. Skin irritation, consisting of erythema, eschar formation, dry and/or flaky skin and small sores were observed at the application site in the 10 and 30 mg/kg groups. No significant irritation was seen in rats in the 3 mg/kg dose group.

The authors of this study therefore concluded that the NOEL is 3 mg/kg. As the intent of the repeated exposure dermal study is to assess systemic toxicity following dermal application of the test material, and as no evidence of systemic toxicity was seen at the high dose, one could conclude that 30 mg/kg did not produce systemic toxicity or neurotoxicity and should be considered a dermal NOEL.