Diphenyl phosphorochloridate

Endpoint summary

Description of key information

LD50 >300 to < 2000 mg/kg bw (Wistar rat, male/female), OECD 423, Cerven (2008)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 May 2008 to 02 July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 210 to 221 g for males and 195 to 244 g for females
- Fasting period before study: 16 to 20 hours
- Housing: 5/sex/cage prior to dosing then 3/sex/cage post dosing in suspended wire mesh cages. Bedding was placed bebeath the cages and changed at least 3 times per week.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64 to 81 °F
- Humidity: 37 to 100 % relative humidity
- Photoperiod: 12 hour light/dark cycle

IN-LIFE DATES: From: 06 May 2008 and 10 June 2008 To: 02 July 2008

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: maximum of 0.37 mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The main test was performed (no data on the toxicity of the test material)

Doses:

50, 300 and 2000 mg/kg bw

No. of animals per sex per dose:

50 mg/kg bw - One female
300 mg/kg bw - One female
2000 mg/kg bw - Three females
2000 mg/kg bw - Three males

A single dose was administered to one female at 50 mg/kg; a single female was then dosed with 300 mg/kg. Three females were dosed with 2000 mg/kg, followed by 3 males being dosed at 2000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of toxicity and mortality at 0.5, 1, 2, 3 and 4 hours post dosing, then once daily thereafter for 14 days. Bodyweights were recorded immediately prior to dosing, then weekly until sacrifice. The animals were weighed again at death or sacrifice.
- Necropsy of survivors performed: Yes. All animals were sacrificed using CO₂ and were examined for gross pathology following termination.
- Other examinations performed: Abnormal tissues were preserved in 10 % neutral buffered formalin for possible future histopathological examination.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All females survived the study.
Two of the three males died (day 1 and 11) during the study.

Clinical signs:

other: No signs of toxicity were observed in the females dosed at 50 and 300 mg/kg bw. One female in the 2000 mg/kg group exhibited wetness of the anogenital area and diarrhoea on the day of dosing. All other females in this group showed no signs of toxicity. Th

Gross pathology:

In one female in the 2000 mg/kg bw group, red areas on the thymus were observed. All other females were found to be normal at necropsy.
Necropsy of the deceased males revealed abnormalities of the lungs, thymus, liver, spleen, gastrointestinal tract as well as wetness of the anogenital area and bloating of the abdomen. The surviving male was found to be normal at necropsy.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 300 mg/kg bw but less than 2000 mg/kg bw in male and female Wistar rats.

Executive summary:

The acute oral toxicity of the test material was evaluated in a study conducted in accordance with the standardised guideline OECD 423 under GLP conditions.

Female Wistar rats were exposed to the test material at 50 mg/kg bw (1 female), 300 mg/kg bw (1 female) and 2000 mg/kg bw (3 females). As all females survived to the end of the study, the LD50 of the test material was therefore confirmed in three male rats dosed with 2000 mg/kg bw.

All females survived the study; two of the three males died (day 1 and 11) during the study. No signs of toxicity were observed in the females dosed at 50 and 300 mg/kg bw. The two males that died exhibited clinical signs of toxicity prior to death. The single surviving male and one female in the high dose group also displayed some signs of clinical toxicity. All other females in this group showed no signs of toxicity.

At necropsy one female dosed with 2000 mg/kg bw group was found to have red areas on the thymus. The two decedents in the male dosing group had abnormalities of the lungs, thymus, liver, spleen, gastrointestinal tract as well as wetness of the anogenital area and bloating of the abdomen at necropsy.

Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 300 mg/kg bw but less than 2000 mg/kg bw in male and female Wistar rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key study by Cerven (2008), the acute oral toxicity of the test material was evaluated in a study conducted in accordance with the standardised guideline OECD 423 under GLP conditions.

Female Wistar rats were exposed to the test material at 50 mg/kg bw (1 female), 300 mg/kg bw (1 female) and 2000 mg/kg bw (3 females). As all females survived to the end of the study, the LD50 of the test material was therefore confirmed in three male rats dosed with 2000 mg/kg bw.

All females survived the study; two of the three males died (day 1 and 11) during the study. No signs of toxicity were observed in the females dosed at 50 and 300 mg/kg bw. The two males that died exhibited clinical signs of toxicity prior to death. The single surviving male and one female in the high dose group also displayed some signs of clinical toxicity. All other females in this group showed no signs of toxicity.

At necropsy one female dosed with 2000 mg/kg bw group was found to have red areas on the thymus. The two decedents in the male dosing group had abnormalities of the lungs, thymus, liver, spleen, gastrointestinal tract as well as wetness of the anogenital area and bloating of the abdomen at necropsy.

Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 300 mg/kg bw but less than 2000 mg/kg bw in male and female Wistar rats.

Justification for selection of acute toxicity – oral endpoint
A single good quality study was available for evaluation. The study was performed in accordance with the standardised guideline OECD 423 under GLP conditions. In accordance with the criteria for assessing data quality as defined in Klimisch et al. (1997), the study was assigned a reliability score of 1.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification with respect to acute oral toxicity as Category 4, H302: Harmful if swallowed.