Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 Aug 1997 to 16 Sept 1997
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Version / remarks:
1981)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
Version / remarks:
(1984)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.3200 (Repeated Dose Dermal Toxicity -21/28 Days)
Version / remarks:
(1996)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 59 NohSan No. 4200 (Guidance on toxicology study data for application of agriculture chemical registration) (1985)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Technical Grade MKH 3586
- Physical state: White powder
- Analytical purity: 98.2%
- Purity test date: October 1997
- Lot/batch No.: 05362/0005
- Expiration date of the lot/batch: 6 months from date of purity testing

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
F: 21 days = total of 17 applications
M: 22 days = total of 18 applications
Frequency of treatment:
Animals were treated on 5 consecutive days (study days 0-4 and 7-11) during the first 2 weeks. For the 3rd week, females were treated on days 14-20 and males were treated on days 14-21.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 200, 500, 1000 mg/kg/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
10 animals/sex/dose group
Control animals:
yes, concurrent no treatment

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Based on:
other: No evidence of toxicity observed
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

OBSERVATIONS:

Clinical signs of toxicity:

No test material related clinical signs of toxicity were observed.

 

Bodyweight and bodyweight gain:

No test material related effects were observed.

 

Food consumption:

No test material related effects were observed.

 

Opthalmoscopic examination:

No test material related effects were observed.

 

Haematology & clinical chemistry:

No test material related effects were observed.

 

Sacrifice and Gross Pathology:

No gross lesions observed at necropsy.

 

Histopathology:

No test material related effects were observed.

 

Organ weights: 

No test material related effects were observed.

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, the NOAEL was 1000 mg/kg/day (the maximum recommended dose, in accordance with current guidelines). No evidence of toxicity was observed.
Executive summary:

MKH 3582 was administeredviathe dermal route to Fischer F344 rats subjected to repeated dermal application under semi-occlusive conditions for 21 days on a 5 day/week basis during weeks 1 and 2 and daily from day 14 to 21. The exposure period was 6 hours/day. Test material doses of 0, 200, 500 and 1000 mg/kg/day were applied to 10 rats/sex/group.

 

The treatment produced no significant clinical signs, no effect on mean body weights or food consumption. No signs of irritation occurred at the application site. No ocular changes were seen and no effect on haematological parameters. Organ weights did not reveal any treatment related effects. Macroscopic post mortem examination did not indicate any treatment related changes.

 

Based on the results of this study, the NOAEL was 1000 mg/kg/day (the maximum recommended dose, in accordance with current guidelines). No evidence of toxicity was observed.