1-chloro-N,N-diethyl-1,1-diphenyl-1-(phenylmethyl)phosphoramine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1993 to April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Standardised method following EC Dir 84/449, although some details are missing in the report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex V B.3, Dir. 84/449/EEC

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

GM102E

IUPAC Name:

GM102E

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

white powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Strain: Sprague Dawley Crl: CD (SD) BR rat
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7-9 weeks
- Weight at study initiation: Males: 225-250g ; Females: 200 - 225 g
- Fasting period before study:
- Housing: individual grill cages
- Diet (e.g. ad libitum): ad libitum, except fasting period prior to dosing
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+/2 2
- Humidity (%): 55% +/- 10
- Air changes (per hr): 20/hour filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 hour cycle (light 7 am-7 pm)

IN-LIFE DATES: From: 25 March 1993 To: 9 April 1993

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

not specified

Remarks:

No details provided in the report.

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10%
- Type of wrap if used: porous gauge dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing. After exposure period, residual substance was wiped off.
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: No details were provided in the report, but the method followed (EC Dir. Annex V, B.3, 94/449) indicates that the powder should be moistened with water.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 Males and 5 females/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical signs observed at 30 min, 2, 4, 6 hours post dosing, then twice daily
weight: twice before dosing (at randomisation and on day 1 before treatment), then on day 8 and 15

- Necropsy of survivors performed: yes (gross pathology)
- Other examinations performed:
clinical signs: yes
body weight: yes
organ weights: no
histopathology: no

Statistics:

No (limit test)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

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: 1

Clinical signs:

other: Signs of toxicity related to dose levels: Clinical signs prior to death of the single female that died on day 2: piloerection and hunched posture. Surviving animals: no clinical signs or altered behaviour observed.

Gross pathology:

Congestion and increased size of the spleen in the single female rats which died during the study.
No changes at the end of the observation period in the other animals.

Other findings:

Signs of toxicity (local):
Local irritation was observed on all animals at the application site up to days 3-11 of the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information EU CLP criteria Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of GM102E in Sprague-Dawley rats was established to be > 2000 mg/kg. One female rat died and local irritation was observed on all animals at the application site up to days 3-11 of the study.

Executive summary:

The acute dermal toxicity of the test item GM102E was investigated in a limit test performed on Sprague Dawley rats. 

The study was performed according to EU method B.3 and in compliance with GLP.

The test item was administered once on 5 males and 5 females using patch applied on the dorsal surface. The test item was tested at the concentration of 2000 mg/kg. No washing was performed and residual substance was wiped off after 24-hour exposure period.

The animals were then observed during 14 days. Clinical signs were observed at 30 min, 2, 4, 6 hours post dosing, then twice daily while weight was measured twice before dosing (at randomisation and on day 1 before treatment), then on day 8 and 15.

One female rat died during the study (day 2). Piloerection and hunched posture were observed before death and congestion and increased size of the spleen were the only findings at autopsy. No general clinical signs were seen in the surviving animals, but they showed erythema, edema, and crusts at the application site starting from days 2-3 and lasting up to days 3-11 of the study. The body weight gain appeared normal. No changes were found at the gross pathology examination performed at the end of the observation period in any rat.

Mortality was confined to only one animal and only local irritation was observed at the application site on the other rats. Thus the LD50 was considered to be > 2000 mg/kg b.w.

Based on these results and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E should not be classified for dermal toxicity.