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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 1994 to July 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- and OECD TG-compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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:

- Physical state: white powder
- Lot/batch No.: 8724
- Expiration date of the lot/batch: November 1994
- Storage condition of test material: no specific requirements

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: Sprague Dawley Crl: CD (SD) BR rats
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7/9 weeks
- Weight at study initiation: Males: 225 - 250 g ; Females: 200 - 225 g
- Fasting period before study: 16 hours
- Housing: 5 animals/sex/cage in T11C air-conditioned room, grill cage 40.5x38.5x18 cm with stainless feeder
- Diet (e.g. ad libitum): ad libitum, GLP 4RF1 Charles River Italia's feed licensee Mucedola s.r.l., Settimo Milanese
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: june 15, 1994 To: july 1, 1994

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.7, 10, 15 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

67 mg/kg, 100 mg/kg, 150 mg/kg

No. of animals per sex per dose:

67 mg/kg : 5 Males and 5 females
100 mg/kg: 5 males
150 mg/kg: 5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 min, 2, 4 ,6 hours post-dosing, then twice a day
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: daily
body weight: day 1, 3, 8 and 14
organ weights, histopathology, other: No

Statistics:

Method of Probit (Bliss-Finney) - AP. Rosiello et al., J. Tox. and Env. Health, 3:797-809, 1977

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

123 mg/kg bw

95% CL:

100.4 - 150.2

Remarks on result:

other: Slope of the mortality curve: 4.33

Mortality:

Male: 67 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 100 mg/kg bw; Number of animals: 5; Number of deaths: 1
Male: 150 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 67 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: Piloerection, hunched posture and diarrhea were observed in animals treated at 67 mg/Kg starting from 2 hours and lasting up to 24 hours after the administration. Animals treated at 100 and 150 mg/Kg showed th

Gross pathology:

Effects on organs: Animals which died showed congestion of the lungs, kidneys, stomach, intestine and thymus and also paleness of the liver and thinning walls with catharral or catharral-hemorrhagic content in the intestine. At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the LD50 to rats was found to be 123 mg/kg.
From this value the substance is to be classified as toxic if swallowed according to the CLP Regulation (EC) No. 1272/2008.

Executive summary:

The acute oral toxicity of the test item GM102E was investigated in a study performed on Sprague Dawley rats at concentrations of 67, 100 and 150 mg/kg.

The test was performed according to OECD guideline 401 and in compliance with GLP.

The test item was administered by gavage to 5 male rats per dose and a further group of 5 females was tested at 67 mg/kg of GM102E. The test item was dissolved in deionized water before administration and the administration volume was kept constant at 10 ml/kg b.w. in all the groups.

All rats were treated after a 16 hours fasting period. The animals were weighed twice before treatment (at randomization and on day 1 just before the study) and on days 3, 8 and 14 after exposure period. They were clinically observed for 14 days following treatment. On day 15 all treated rats were killed by excision of the femoral arteries, after i.p. overdosage anesthesia with 5% sodium pentobarbital. Animals which died and animals killed at the end of the study were submitted to a thourough autopsy.

Piloerection, hunched posture and diarrhea were clinically observed in animals treated at the lowest dose (67 mg/kg) starting from 2 hours and lasting up to 24 hours after the test item administration. Animals treated at the highest doses (100 and 150 mg/kg) showed the same clinical signs and, in addition, sedation and/or hypoactivity and sporadic cases of shallow breathing, chromodacryorrhea and pallor of the skin and apparent mucosae. These signs started from 30 minutes – 4 hours and lasted up to 6 hours – day 3 of the study. Recovery of all surviving rats was achieved within days 2 – 4 of the study.

Body weight gain resulted unaffected by treatment in animals treated at the lowest dose. Surviving male rats treated at 100 and 150 mg/kg showed decrease in body weight or low body weight gain at the day 3 weighing. Body weight gain returned to normal at the subsequent recordings.

At the autopsy, animals which died showed congestion of the lungs, kidnays, stomach, intestine and thymus and also paleness of the liver and thinning walls with catharral or catharral-hemorrhagic content in the intestine.

At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.

One male treated at 100 mg/kg and 4 males treated at 150 mg/kg died within 2 hours of treatment. No animals treated at 67 mg/kg died. The LD50 was calculated to be 122.8 mg/kg with 95% confidence limits of 100.4 – 150.2 mg/kg.

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 be classified as toxic by ingestion (Acute tox. Category 3, H301).