Bis(cyclohexyl)ammonium(2S)-2-{[(benzyloxy)carbonyl]amino}-3,3-dimethylbutanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been conducted fully GLP-compliant according to the relevant OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-250-9

EC Name:

-

Cas Number:

62965-37-1

Molecular formula:

C26H42N2O4

IUPAC Name:

(2S)-2-{[(benzyloxy)carbonyl]amino}-3,3-dimethylbutanoic acid; N-cyclohexylcyclohexanamine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: CD (Crl:CD BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks (at test item administration)
- Weight at study initiation: 224-312 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 1 % aqueous methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: app. 50x50 mm (10% of the total body surface area)
- Type of wrap if used: porous gauze held in place with a nonirritating dressing, covered by a waterproof dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water (30 - 40 °C) and blotted dry with absorbent paper
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.w.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (mortality, clinical signs): soon after dosing and twice daily thereafter
- Frequency of weighing: day 0 (prior to dosing), day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy, organ weights, histopathology

Results and discussion

Preliminary study:

LD50 dermal >2000 mg/kg body weight

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels:
None.

Body weight:

On Day eight a low bodyweight gain was recorded for three females and a bodyweight loss was recorded for one other female. All other animals
were considered to have achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

Effects on organs:
None.

Other findings:

Signs of toxicity (local):
After bandage removal a small area of scab formation was noted in two males and one female and for one other female from day 6, and another female from day 8. These reactions had all resolved by day 11. In addition very slight irritation was observed in two females on day 3. These reactions had resolved by day 4.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dermal dose (LD50) to rats of VRT-126017 dcha was demonstrated to be greater than 2000 mg/kg bodyweight.
VRT-126017 dcha is in Category 3 according to the EPA Health Effects Test Guidelines OPPTS 870.1000 Acute Toxicity testing EPA 712-C-98-189 August 1998.