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Administrative data

Description of key information

Two reliable studies are available for the acute toxicity endpoint by oral route. These studied showed that DPTU is not harmful by oral route with a LD50 higher than 2000 mg/kg.
An acute toxicity study by dermal route is available with DPTU : no mortality was observed at 2000 mg/kg on rats therefore DPTU is considered as not harmful by dermal route (LD50 > 2000 mg/kg).
There are no data on acute toxicity by inhalation.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study comparable to guideline study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male and female rats were exposed to one only dose of DPTU (2000 mg/kg bw). Mortality and clinical signs were observed during 14 days.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: around 185g (males) and around 170g (females)
Route of administration:
oral: unspecified
Vehicle:
physiological saline
Remarks:
Suspension in physiologic saline with the addition of 2% Cremophor EL
Details on oral exposure:
Volume administered: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
one group = 5 males + 5 females
Control animals:
no
Details on study design:
The animals were observed for clinical signs, mortality, body weights and gross pathological changes.
Post dose observation period: 14 days
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: (no mortality)
Mortality:
no mortality
Clinical signs:
Apathy and piloerection were observed. Onset of these symptoms was about 30min after administration but by day 2, all animals were free of clinical signs.
Body weight:
no effects
Gross pathology:
no effects
Other findings:
NECROPSY FINDINGS: no abnormalities
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC 1272/2008 (CLP)
Conclusions:
No mortality is observed at 2000 mg/kg bw. The acute oral LD50 for male and female rats is > 2000 mg/kg bw.
Executive summary:

One group of 5 male and 5 female young adult rats (185/170 g) was dosed at 2000 mg/kg. The animals were obiserved for mortality, body weights, clinical signs and gross pathological changes through day 14.

No mortality was observed. Clinical signs included aptathy and piloerection. Onset of symptoms was about 30 min porst administration. By day 2, all animals were free of clinical signs. Final necropsy at day 14 revealed no abnormalities. The acute oral LD50 for male and female rats is > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Bombard's study is a reliable study with a klimisch score of 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:
03 February 2012 - 14 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.
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
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: the males had a mean body weight of 348 g (range: 341 g to 359 g) and the females had a mean body weight of 242 g (range: 224 g to 257 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed by five from the same sex and group in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: 14 February 2012 to 14 March 2012.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24 h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

Duration of exposure:
single exposure (24 hours)
Doses:
2000 mg/kg.
No. of animals per sex per dose:
5 animals per group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
Very slight erythema was recorded at the application site of one female from day 11 to day 13.
No cutaneous reactions were observed in males.
Body weight:
When compared to historical control data, a lower body weight gain was noted in the most of females during whole study and in 3/5 males between days 8 and 15. In addition, a body weight loss of -2 g was noted in females between days 8 and 15.
Gross pathology:
No macroscopic changes were seen at necropsy following a single dermal application of test item in rats at the dose-level of 2000 mg/kg.
Other findings:
no
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC 1272/2008
Conclusions:
The dermal LD50 of the test item, 1,3 Diphenyl 2 thiourea, was higher than 2000 mg/kg in rats.
Therefore, the test item is not classified as harmful or toxic toxic by dermal route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item, 1,3‑Diphenyl‑2‑thiourea, following a single dermal application to rats.

This study was conductedaccording to OECD (No. 402, 24th February 1987) and EC (No. 440/2008, Part B.3, 30 May 2008) guidelines, and in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item, 1,3‑Diphenyl‑2‑thiourea,was applied in its original form to the skin of five female then five male Sprague‑Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi‑occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

 

Results

No unscheduled deaths occurred during the study.

No clinical signs indicative of systemic toxicity were observed in any animals.

Very slight erythema was recorded at the application site of 1/5 females from days 11 to 13. No cutaneous reactions were observed in males.

Lower body weight gain was recorded in the most of animals.

No macroscopic changes were seen at necropsy.

 

Conclusion

The dermal LD50of the test item, 1,3‑Diphenyl‑2‑thiourea, was higher than 2000 mg/kg in rats.

Therefore, the test item is not classified as harmful or toxic by dermal route according to the criteria of CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Queudot's study is a reliable study with a klimisch score of 1.

Additional information

Acute toxicity studies by oral route :

In the key study (Bombard 1992), one group of 5 male and 5 female young adult rats (185/170 g) was dosed at 2000 mg/kg. The animals were observed for mortality, body weights, clinical signs and gross pathological changes through day 14.

No mortality was observed. Clinical signs included apathy and piloerection. Onset of symptoms was about 30 min post administration. By day 2, all animals were free of clinical signs. Final necropsy at day 14 revealed no abnormalities. The acute oral LD50 for male and female rats is > 2000 mg/kg bw.

The supporting study (Dieke 1947) gave the same results : DPTU was administered to norway rats and the LD50 for DPTU is higher to 1500 mg/kg bw. No mortality was observed in this dose.

Acute toxicity study by dermal route (Queudot 2012) :

The objective of this study was to evaluate the potential toxicity of the test item, 1,3 -Diphenyl-2-thiourea, following a single dermal application to rats. This study was conductedaccording to OECD (No. 402, 24th February 1987) and EC (No. 440/2008, Part B.3, 30 May 2008) guidelines, and in compliance with the principles of Good Laboratory Practice.

The test item, 1,3 -Diphenyl-2-thiourea,was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours. Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded on day 1 and then on days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

No unscheduled deaths occurred during the study. No clinical signs indicative of systemic toxicity were observed in any animals.

Very slight erythema was recorded at the application site of 1/5 females from days 11 to 13. No cutaneous reactions were observed in males.

Lower body weight gain was recorded in the most of animals. No macroscopic changes were seen at necropsy.

The dermal LD50 of the test item, 1,3 -Diphenyl-2-thiourea, was higher than 2000 mg/kg in rats. Therefore, the test item is not classified as harmful or toxic by dermal route according to the criteria of CLP Regulation.


Justification for selection of acute toxicity – oral endpoint
Bombard study is a reliable study with a klimisch score of 1, because it is comparable to a guideline study, and it is the most recent study.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available to evaluation the acute toxicity of DPTU by dermal route.

Justification for classification or non-classification

No classification is required for the acute toxicity of DPTU according to the Regulation EC 1272/2008 or the Directive 67/548/EEC.

Oral and dermal LD50 are higher than 2000 mg/kg. And no data is available by inhalation.