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Administrative data

Description of key information

In an acute dermal toxicity study with rats, an LD50 >2000 mg/kg bw for Accelerator (PT 25E or PT 25E/2) was determined.

In an acute oral toxicity test performed according to the OECD guideline, the LD50 of the test substance was found to be 619 mg/kg bw.

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:
October 9th - November 9th, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Remarks:
issued 31JAN1994
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK)
- Age at study initiation: 5-8 weeks
- Weight at study initiation: males 137 - 181g; females 132 - 154g
- Fasting period before study: o/n before dosing and 2 hours after dosing
- Housing: group-housed (up to 5 of same sex)
- Diet: ad libitum (Rat and mouse expanded diet No.1, special diets services limited, Witham, Essex, UK)
- Water: ad libitum
- Acclimation period: minimal 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 44-57
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.86 ml/kg
Doses:
500, 1000, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded on the day of dosing and on days 7 and 14.
- Necropsy of survivors performed: yes (gross pathology)
- Other examinations performed: clinical signs, at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily.
Statistics:
The LD50-value was calculated using a probit method of Finney, DJ: "Probit Analysis", 1971, Cambridge University Press. The LD50 and 95% confidence limits were calculated for males only.
Preliminary study:
No mortality was observed in the range-finding study.
Sex:
male
Dose descriptor:
LD50
Effect level:
619 mg/kg bw
Based on:
test mat.
95% CL:
>= 305 - <= 1 256
Remarks on result:
other: Male animals were considered to be more sensitive to the test material than female animals.
Mortality:
At 2000 mg/kg bw, all males died and 3/5 females.
At 1000 mg/kg bw, 3/5 males died (only males treated) and at 500 mg/kg bw 2/5 males died (at these dosages, only males were treated).
Mortality occurred within half an hour after dosing.
Clinical signs:
Common signs of systemic toxicity noted in the surviving animals were hunched posture, decreased respiratory rate and laboured respiration with additional signs of ataxia. Lethargy was commonly noted in males treated with 1000 mg/kg and females treated with 2000 mg/kg bw. Isolated incidents of systemic toxicity noted in two females treated with 2000 mg/kg bw were pilo-erection and/or pallor of the extremities.
Clinical signs disappeared one or two days after dosing in the surviving animals.
Body weight:
Surviving animals showed expected gain in body weight during the study.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Cat. 4 according to EC Regulation 1272/2008
Conclusions:
In an acute oral toxicity test performed according to the OECD guideline, the LD50 of BISOMER PTE was found to be 619 mg/kg bw.
Executive summary:

An acute oral toxicity test was performed according to the OECD guideline, with male and female rats.

At the starting dose (2000 mg/kg bw) all males and 3/5 females died. At the lower doses only males were treated. At 1000 mg/kg bw 3/5 rats died, at 500 mg/kg bw 2/5 rats died. Death occurred in all animals within 0.5 hours after dosing. The surviving animals showed hunched posture, decreased respiratory rate and laboured respiration with additional signs of ataxia. Lethargy was commonly noted in males treated with 1000 mg/kg and females treated with 2000 mg/kg bw. These clinical signs disappeared within one or two days after exposure. Surviving animals showed expected gain in body weight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Based on an LD50 of 619 mg/kg bw, BISOMER PTE is classified for acute oral toxicity cat. 4 according to EC regulation No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
619 mg/kg bw
Quality of whole database:
The study is conducted in accordance with the OECD guideline and GLP principles (reliability 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 28th - March 14th, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
issued 19 May 2011
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean; at start males: 266-285g, females: 185-209g
- Housing: Individually housed in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 FEB 2013 to 14 MAR 2013
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research and on test substance data supplied by the sponsor.

Dose volume: 2000 mg/kg (10 mL/kg) body weight

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 75ºC for a maximum of 17 minutes. The test substance formulation was allowed to cool down to a temperature of maximally 40ºC prior to dosing.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: None
Statistics:
None.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, piloerection and/or chromodacryorrhoea were noted in all males and three females on Days 1 and/or two. Hypothermia was noted in one male on Day 2. No signs of irritation were seen in the treated skin-area of the animals during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
Two males showed many reddish foci in the thymus and three females showed enlarged size of mandibular lymph nodes during macroscopic post mortem examination. No abnormalities were found in the other animals.
Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to EC Regulation 1272/2008
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. Accelerator (PT 25E or PT 25E/2) was applied occlusively at 2000 mg/kg bw for 24 hours. No mortality occurred. No unexpected changes in body weight gain were reported. Hunched posture, piloerection and/or chromodacryorrhoea were noted in all males and three females on Days 1 and/or two. Hypothermia was noted in one male on Day 2. Two males showed many reddish foci in the thymus and three females showed enlarged size of mandibular lymph nodes during macroscopic post mortem examination. No abnormalities were found in the other animals.

Based on these results, the test substance has an acute LD50 > 2000 mg/kg bw and is not classified for acute dermal toxicity according to EC regulation No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Study was performed according to OECD guideline and GLP principles (reliability 1).

Additional information

Acute oral testing:

An acute oral toxicity test was performed with BISOMER PTE according to the OECD guideline, with male and female rats. At the starting dose (2000 mg/kg bw) all males and 3/5 females died. At the lower doses only males were treated. At 1000 mg/kg bw 3/5 rats died, at 500 mg/kg bw 2/5 rats died. Death occurred in all animals within 0.5 hours after dosing. The surviving animals showed hunched posture, decreased respiratory rate and laboured respiration with additional signs of ataxia. Lethargy was commonly noted in males treated with 1000 mg/kg and females treated with 2000 mg/kg bw. These clinical signs disappeared within one or two days after exposure. Surviving animals showed expected gain in body weight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

An acute oral toxicity test was conducted with female rats following OECD guidelines according to GLP principles. No mortality occurred. No unexpected changes in body weight gain were reported, and no treatment related clinical signs were observed. Gross macroscopy showed no alterations in any of the major organs of the examined animals.

Acute dermal testing:

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. Accelerator (PT 25E or PT 25E/2) was applied occlusively at 2000 mg/kg bw for 24 hours. No mortality occurred. No unexpected changes in body weight gain were reported. Hunched posture, piloerection and/or chromodacryorrhoea were noted in all males and three females on Days 1 and/or two. Hypothermia was noted in one male on Day 2. Two males showed many reddish foci in the thymus and three females showed enlarged size of mandibular lymph nodes during macroscopic post mortem examination. No abnormalities were found in the other animals.


Justification for selection of acute toxicity – oral endpoint
A reliable acute oral toxicity study is used.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

Based on the observations in a reliable oral acute toxicity study, the test substance has an acute oral LD50 of 619 mg/kg bw and is classified Cat 4 for acute oral toxicity according to EC regulation No 1272/2008.

Based on the results of an acute dermal toxicity test, Accelerator (PT 25E or PT 25E/2) has an acute LD50 > 2000 mg/kg bw and is not classified for acute dermal toxicity according to EC regulation No 1272/2008.