polymeric zinc propylenebis(dithiocarbamate);propineb (ISO)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010/03 to 2010/06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

polymeric zinc 1,2-propylenebis(dithiocarbamate)

EC Number:

620-365-5

Cas Number:

9016-72-2

IUPAC Name:

polymeric zinc 1,2-propylenebis(dithiocarbamate)

Test material form:

solid

Remarks:

Powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Acclimatization period: at least 5 days.
- Age: 8 weeks Approximately.
- Water: tap water, ad libitum
- Weight at dosing: 372-387 g males and 217-242 g females.
- Housing: During the acclimation period, one to seven animals of the same sex were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). During the treatment period, the animals were housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm). Each cage contained autoclaved sawdust.

ENVIRONMENTAL CONDITIONS
- Temperature (22 ± 2°C):
- Humidity (30 to 70%):
- Air changes (per hr): Approximately 12
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: 9 to 24 March 2010

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

A single dose of 2000 mg/kg of the propineb in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of purified water) and then applied to an area of the skin representing approximately 10% of the total body surface of the animals, calculated according to Meeh's formula (i.e. approximately 5 cm x 7 cm for the males and 5 cm x 6 cm for the females).

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

previous non GLP study, in which the cutaneous LD50 of the test item was higher than 2000 mg/kg. Therefore, a limit test was carried out by administering 2000 mg/kg to one group of ten animals (five males and five females).

On the day before treatment, the dorsal area of each animal was clipped (i.e. approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females) using an electric clipper. Only animals with healthy intact skin were used for the study.

Statistics:

The data did not warrant statistical analysis

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred at 2000 mg/kg bw, the only dose level tested.
The dermal LD50 for males was > 2000 mg/kg bw
for females was > 2000 mg/kg bw
for the combined sexes was > 2000 mg/kg bw.

Clinical signs:

other: other: No systemic clinical signs were noted in any animal. A yellow coloration of the skin was noted in all animals between day 2 and day 15. This coloration masked the evaluation of cutaneous reactions in all animals on day 2, in 2/5 males and 1/5 femal

Gross pathology:

No abnormalities were observed at gross necropsy.

Any other information on results incl. tables

Table 1

Doses, toxicological results* / animals treated

Dose (mg/kg bw)	Male	Female	Combined
2000	0/0/5	0/0/5	0/0/10

* :   number of animals which died spontaneously and/or were sacrificed in moribund state/number of animals with signs of toxicity/total number of animals used per group

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The objective of this study was to evaluate the toxicity of the test item, Propineb,
following a single dermal application to rats according to OECD (No. 402, 24th February 1987)
and Commission Regulation (EC) (No. 440/2008, Part B.3, 30 May 2008) guidelines.
The study was conducted in compliance with the principles of Good Laboratory Practice. The test item, in its original form, was applied for 24 hours to the skin of one group of
ten Sprague-Dawley rats (five males and five females) treated at the dose-level of 2000 mg/kg.
The test site was then covered by a semi-occlusive dressing. The dermal LD50 of the test item, Propineb, was higher than 2000 mg/kg bw in male and female rats.

Executive summary:

The objective of this study was to evaluate the toxicity of the test item, Propineb (AE F074263), following a single dermal application to rats according to OECD (No. 402, 24th February 1987) and Commission Regulation (EC) (No. 440/2008, Part B.3, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice.

The test item, in its original form, was applied for 24 hours to the skin of one group of ten Sprague-Dawley rats (five males and five females) treated at the dose-level of 2000 mg/kg bw. The test site was then covered by a semi-occlusive dressing.

Mortality, clinical signs and body weight gain were checked for a period of 14 days following the single application of the test item. On completion of the observation period, the animals were sacrificed then subjected to a macroscopic post-mortem examination. The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

No deaths and no systemic clinical signs were observed during the study. A yellow coloration of the skin was noted in all animals between day 2 and day 15. This coloration masked the evaluation of cutaneous reactions in all animals on day 2, in 2/5 males and 1/5 females from day 3 until day 5 and in one male until day 9. An erythema was observed in 1/5 males on day 3 and 1/5 females from day 3 until day 5.

When compared to CIT historical control data, a lower body weight gain was noted in 1/5 females between day 1 and day 8 (9 g vs. 25 ± 11 g, in control data base) and in 4/5 males between day 1 and day 8 (17 to 37 g vs. 47 ± 7 g, in control data base) and between day 8 and day 15 (36 to 42 g vs. 51 ± 8 g, in control data base). The body weight gain of the other animals was not affected by treatment with the test item. No apparent abnormalities were observed at necropsy in any animal.

Under the experimental conditions of this study, the dermal LD50 of the test item, Propineb, was higher than 2000 mg/kg in rats. According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), concerning the potential toxicity by dermal route, the test item should not be classified.