Phenyl phosphorodichloridate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

1997-02-21

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl phosphorodichloridate

EC Number:

212-220-6

EC Name:

Phenyl phosphorodichloridate

Cas Number:

770-12-7

Molecular formula:

C6H5Cl2O2P

IUPAC Name:

phenyl dichlorophosphate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Females (if applicable) nulliparous
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: male 206 to 242 g and female 200 to 224 g
- Fasting period before study: yes
- Housing: in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): Free access
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22°C
- Humidity (%): 48 to 63 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 121/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Range finding: 1000 and 2000 mg/kg
Main test: 707, 1000 and 1414 mg/kg

No. of animals per sex per dose:

range finding: 1 male and 1 femlae per dose
Main test: 5 female per dose and 5 male at the low dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 minutes, 1h, 2h and 4h the first day of dosing and once a day during fourteen days. The body weight was measureed on days 1, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Results and discussion

Preliminary study:

2/2 animals dead at 2000 mg/kg
0/2 animals dead at 1000 mg/kg

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

843 mg/kg bw

Based on:

test mat.

95% CL:

> 612 - < 1 161

Mortality:

Male: 5/5 deaths 30 minutes after dosing at 707 mg/kg
Female: 2/5 deaths within 14 days at 707 mg/kg, 2/5 deaths at 1000 mg/kg and 5/5 days deaths at 200 mg/kg

Clinical signs:

other: Clinical signs of toxicity noted in females treated with 707 mg/kg or greater were ataxia, hunched posture, lethargy and decreased respiratory rate with incidents of laboured respiration. Additional signs of systemic toxicity noted in females treated with

Gross pathology:

Common abnormalities noted at necropsy of animals that died or were killed in extremis during the study were dark liver or green discolouration of the liver, dark kidneys and haemorrhage, severe haemorrhage or thickening of the gastric mucosa. Severe haemorrhage of the small and 1arge intestines was noted at necropsy of females treated with 1000 or 1414 mgikg and males treated with 707 mg/kg that died during the study.
Haemorrhagic or abnormally red lungs were noted at necropsy of females treated with 707 or 1414 mg/kg that died during the study. Haemorrhage of the non-glandular epithelium of the stomach was noted at necropsy of males treated with 707 mg/kg and females treated with 1414 mg/kg that died during the study. Areas of green-coloured necrosis on the gastric mucosa were noted at necropsy of one female treated with 707 mg/kg that was killed in extremis during the study.
Abnormalities noted at necropsy of females treated with 707 mwkg that were killed at the end of the study were haemorrhagic lungs, dark liver, dark kidneys and white foci on the gastric mucosa.
No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Any other information on results incl. tables

Mortality data in the main study

Dose (mg/kg)	Sex	Number of animals	Deaths during day od dosing (hour)				Deaths during day od dosing (days)								deaths	%
			½	1	2	4	1	2	3	4	5	6	7	8-14
707	Male	5	5	-	-	-	-	-	-	-	-	-	-	-	5/5	100
	Female	5	0	0	0	0	0	0	1	0	0	0	0	1*	2/5	40
1000	Female	5	2	0	0	0	0	0	0	0	0	0	0	0	2/5	40
1414	Female	5	3	2	-	-	-	-	-	-	-	-	-	-	5/5	100

* Killed in extremis day 9

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the Phenyl dichlorophosphate for the female was 843 mg/kg

Executive summary:

Acute oral LD50 of Phenyldichlorophosphate has been determined according to EU B.1 method and OECD test guideline 401 in compliance with GLP. The acute oral LD50 of Phenyldichlorophosphate was determined to be equal to 843 mg/kg for the female.