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Description of key information

In a well conducted acute oral toxicity study (Safepharm Laboratories, 1982) conducted with DTPMP-7Na using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg). Taking the results of this study together with an additional study conducted at SafePharm Laboratories (1982b) with the same salt, an oral LD50 of 10 ml/kg < LD50 < 15 ml/kg is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD50 < 8757 mg active salt/kg bw).

In an acute dermal toxicity study (Safepharm Laboratories, 1982) conducted with DTPMP-7Na using a protocol comparable to OECD 402, and to GLP, the LD50 for the sodium salt of DTPMP was > 10 ml/kg bw (> 5838 mg active salt/ kg bw, equivalent to > 4602 mg parent acid) in rats. There are no data for the inhalation route.

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:
19.08.1982 to 02.09.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Principles of method if other than guideline:
Method: other: Safepharm protocol (number GM 11/80/21A). Broadly compatible with the now deleted OECD 401.
GLP compliance:
yes
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: A. Tuck and Sons Ltd., Battlesbridge, Essex, UK.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: Males: 98-120 g; Females: 90-115 g
- Fasting period before study: Overnight prior to dosing
- Housing: Groups of five in polypropylene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 65-72
- Air changes (per hr): Approx. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.08.1982 to 02.09.1982
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
3 and 10 ml/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations and weighing on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abnormal organs.
Statistics:
Not required as no deaths occurred.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Mortality:
No deaths occurred.
Clinical signs:
At 3.0 ml/kg bw: General signs of toxicity in all animals in this study included pilo-erection, abnormal body carriage (hunched posture) and lethargy for the first day after dosing. From day 2 after dosing, no abnormal symptoms observed.  No deaths. 
At 10.0 ml/kg bw: General signs of toxicity in all animals in this study included pilo-erection, abnormal body carriage (hunched posture), lethargy and decreased respiratory rate shortly after dosing.  All male and two female test animals also suffered ptosis.  From day 4 after dosing, no abnormal symptoms observed in any animal.  No deaths.  No macroscopic abnormalities observed at necropsy.
Body weight:
Apart from one male in the 3 ml/kg bw groups, all body weights were considered normal.
Gross pathology:
No abnormal findings.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm study 92/8208 (1982), an LD50 of 10 ml/kg < LD50 < 15 ml/kg is determined for the test substance in the rat (equivalent to 5838 mg < LD50 < 8757 mg active salt/kg bw).
Executive summary:

In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm Laboratories study 92/8208 (1982b), an LD50 of 10 ml/kg < LD50 < 15 ml/kg is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD50 < 8757 mg active salt/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 838 mg/kg bw

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:
03.08.1982 to 17.08.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
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: A. Tuck and Sons Limited, Battlesbridge, Essex, UK.
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: Males: 221-235 g; Females: 202-234 g.
- Fasting period before study: No
- Housing: Individually (during exposure) or in groups of five in polypropylene cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 65-75
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 03.08.1982 to 17.08.1982
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal, lateral and ventral regions.
- % coverage: No data
- Type of wrap if used: Elastic adhesive bandage backed with aluminium foil.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw
Duration of exposure:
24 hours
Doses:
10 ml/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Skin responses were evaluated 0.5, 1, 2, 3, 4, and 5 hours after removal of the patch and residual test substance, and each day for 14 days.  Body weight was measured on days 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination.
Statistics:
Not required as no deaths occurred.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Mortality:
No deaths.
Clinical signs:
Lethargy was observed in two animals (one male and one female) on the day of dosing.  From four hours after dosing, no abnormal symptoms observed in any animal. 
Body weight:
Body weight were within normal limits throughout the test period.
Gross pathology:
No abnormal findings.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study (reliability score 1) conducted using a protocol comparable to OECD 402, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw (>5838 mg active salt/kg bw, equivalent to >4602 mg parent acid) in rats.
Executive summary:

In an acute dermal toxicity study (reliability score 1) conducted using a protocol comparable to OECD 402, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw (>5838 mg active salt/kg bw, equivalent to >4602 mg parent acid) in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 838 mg/kg bw

Additional information

The most reliable studies were selected as the key studies. Available supporting studies also showed sodium salts of DTPMP to be of low acute toxicity.

Justification for classification or non-classification

Based on the available data for DTPMP (5-7Na), no classification for acute toxicity is required according to Regulation (EC) No 1272/2008.