Reaction products of diazotized 2-amino-4-(methylsulfonyl)-phenol with 2-(3-Chlorophenyl)-2,4-dihydro-5-methyl-3H-pyrazol-3-one and Methyl-7-hydroxy-1-naphthylcarbamate – and chromium (III) 2:1, salted by ammonium, sodium and acid

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment. No purity of test substance was given. Only 1 animal per sex was used per treatment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1966

Report date:

1966

Materials and methods

Principles of method if other than guideline:

Albino rabbits were divided into 3 groups, namely 2 test groups (10, 50 mg/kg bw) and 1 control group (1 ml/kg bw dimethyl phthalate). Per dose 1 male and 1 female rabbit was treated each on intact and abraded skin (in summary 2 males and 2 females per dose). In the control group number of animals was doubled. The test substance was applied in dimethyl phthalate. Applications were administered five consecutive days per week for three weeks. The material was permitted to remain in contact with the animals' skins for six hours per day, the backs being wiped at the end of each daily exposure. Fifteen exposures were made. Control animals were handled in a manner similar to the test animals.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Irgacet Brown 2GL

IUPAC Name:

Irgacet Brown 2GL

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Acclimation period: 2 weeks

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: dimethyl phthalate

Details on exposure:

The backs of the animals were wiped after each daily exposure.

Duration of treatment / exposure:

6 hours

Frequency of treatment:

five days a week, for a total of 3 weeks (15 exposures)

Doses / concentrations

Remarks:

Doses / Concentrations:
10, 50 mg/kg bw
Basis:
nominal per unit body weight

No. of animals per sex per dose:

Intact skin:
Group 1 (10 mg/kg bw): 1 female and 1 male rabbit
Group 2 (50 mg/kg bw): 1 female and 1 male rabbit
Control group (1 mL dimethyl phthalate/kg bw): 2 female and 2 male rabbits
Abraded skin:
Group 1 (10 mg/kg bw): 1 female and 1 male rabbit
Group 2 (50 mg/kg bw): 1 female and 1 male rabbit
Control group (1 mL dimethyl phthalate/kg bw): 2 female and 2 male rabbits

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

OBSERVATIONS: Comparison of general appearance and behaviour was reported without details.
DERMAL IRRITATION: Yes, at least after termination of study.
BODY WEIGHT: Yes
- Time schedule for examinations: Twice weekly, during the exposure period
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to study and at termination of study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All study animals
- Parameters checked: Hb, RBC, WBC (differential count)
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Examined organs and tissues: Brain, Thyroid, Adrenal, Lung, Heart, Spleen, Bone Marrow, Stomach, Intestines, Pancreas, Liver, Kidney, Testes, Skeletal Muscle, Skin

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY:
No mortality occured. In all respects the treated groups behaved in a manner similar to the controls based upon gross observation.

HAEMATOLOGY:
Hematological findings in the experimental animals did not differ significantly from those of the control animals. All were within normal limits for the species.

ORGAN WEIGHTS:
No pattern of response attributable to the dosages applied was evident. Neither the sex of the animals, nor the condition of the skin at application (abraded or intact) appeared to have any significant effect upon the experimental animals' weight changes as compared to those of the control animals.

GROSS and HISTOPATHOLOGY:
There was no gross or histologic evidence of specific organ injury in any of the treated animals as compared to the controls which could be attributed to effect of the material under study. The skins at the site of drug application revealed no evidence of inflammation. A low incidence of those incidental and parasitic diseases often found in experimental rabbits was observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified