ethametsulfuron-methyl (ISO); methyl 2-[(4-ethoxy-6-methylamino-1,3,5-triazin-2-yl)carbamoylsulfamoyl]benzoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A single dose of the test substance was applied to the shaved, abraded skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were weighed and observed for 14 days (weekends excluded) following removal of the test material. At the end of the observation period, 2 male and 2 female rabbits were killed and examined for gross and histomorphologic changes.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 002

Cas Number:

97780-06-8

Test material form:

solid

Details on test material:

-Purity: 96.8%

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Buckshire Corporation, Perkasie, Pennsylvania
- Females (if applicable) nulliparous and non-pregnant: No data are provided in the report
- Age at study initiation: Young adult
- Weight at study initiation: The rabbits weighed between 2366 and 2927 grams on the day of dosing
- Fasting period before study: No data are provided in the report
- Housing: The rabbits were housed singly in suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow® #5322
- Water (e.g. ad libitum): Source of water was not provided in the report
- Acclimation period: Two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 2°C
- Humidity (%): 50% ± 10%.
- Air changes (per hr): No data are provided in the report
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: The aliquot of test material designated for an animal was moistened with dimethyl phthalate to form a paste

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 190 square centimeters
- % coverage: 190 square centimeters is approximately equal to 10 percent of
the total body surface area of rabbits in the 2 - 3 kg body weight range
- Type of wrap if used: The rabbits were then wrapped with successive layers of plastic film, stretch gauze bandage and elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess test material was wiped from the animals' backs with dry paper towels
- Time after start of exposure: Approximately 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg of body weight
- Concentration (if solution): Paste
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male and 5 female rabbits per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed approximately every other day (weekends excluded) until the 14th day post application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross and histopathology

Statistics:

No

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no deaths at highest dose tested

Mortality:

No rabbits died within 14 days after application of 2000 mg/kg of test substance

Clinical signs:

other: Clinical observations during the study were limited to body weight effects; no other clinical signs of toxicity were observed in any rabbit throughout the study

Gross pathology:

No gross or microscopic compound-related effects' were observed in rabbits killed 14 days after treatment

Other findings:

One rabbit exhibited severe erythema 1 day after application; the skin appeared normal at 3 days. No other dermal irritation was present throughout the remainder of the test

Any other information on results incl. tables

Individual body weights (g) of male rabbits after dermal exposure to the test substance

 

Animal #	Initial body weight	Body weight on day 1	Body weight on day 3	Body weight on day 6	Body weight on day 8	Body weight on day 10	Body weight on day 13	Body weight on day 14
19881	2524	2415	2569	2711	2766	2808	2961	3035
19882	2460	2427	2475	2634	2687	2724	2723	2769
19883	2366	2273	2379	2409	2537	2611	2694	2734
19884	2563	2514	2634	2643	2745	2852	2939	2950
19885	2927	2904	2975	2959	3023	3050	3074	3071

 

Individual body weights (g) of female rabbits after dermal exposure to the test substance

 

Animal #	Initial body weight	Body weight on day 1	Body weight on day 3	Body weight on day 6	Body weight on day 8	Body weight on day 10	Body weight on day 13	Body weight on day 14
19840	2746	2714	2888	2818	2920	2978	2973	3059
19841	2927	2900	3048	3096	3132	3190	3198	3102
19842	2862	2602	2861	2934	2972	3058	3123	3115
19843	2508	2508	2652	2611	2731	2756	2771	2825
19844	2609	2557	2696	2704	2856	2991	2986	2992

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for male and female New Zealand White rabbits was greater than 2000 mg/kg of body weight.

Executive summary:

A single dose of the test substance was applied to the shaved, abraded skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were weighed and observed for 14 days (weekends excluded) following removal of the test material. At the end of the observation period, 2 male and 2 female rabbits were killed and examined for gross and histomorphologic changes.

 

No rabbits died within 14 days after dosing. Slight or moderate weight losses (up to 9% of initial body weight) occurred in the rabbits the day after application of the test material. One rabbit exhibited severe erythema 1 day after application; the skin appeared normal at 3 days. No other dermal irritation was present throughout the remainder of the test. No gross or microscopic compound-related effects' were observed in rabbits killed 14 days after treatment.

 

Under the conditions of this test, the skin absorption LD50 was greater than 2000 mg/kg of body weight, the highest dose tested.