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Administrative data

Description of key information

In the key acute oral toxicity study, DTPMP-H (58% w/w solution) was tested (Younger Laboratories, 1971). The maximum dose tested by the oral route was 10000 mg/kg bw of the formulation. The acute oral LD50 was determined to be 7180 mg/kg bw (equivalent to 4164 mg active acid/kg bw). Decedent animals died within one day of treatment, and had acute gastrointestinal inflammation and slight liver discoloration.

In the key dermal toxicity study (Younger Laboratories, 1971) using DTPMP-H (58% w/w solution) there were no deaths when the formulation was applied at the maximum dose of 7940 mg/kg bw (24 h contact time, under occlusion), equivalent to an LD50 of >4605 mg active acid/kg bw. This is a non-GLP study, performed to standards acceptable at the time and provides sufficient evidence of the low acute dermal toxicity of the acid.

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Conducted prior to the adoption of OECD test guideline.
Principles of method if other than guideline:
Method: other: Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: Males: 190-250 g. Females: 200-235 g.
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: No data

Doses:
5010, 6310, 7940 and 10000 mg/kg bw
No. of animals per sex per dose:
5010 mg/kg bw : 2 male, 3 female; 6310 mg/kg bw: 3 male, 2 female; 7940 mg/kg bw: 2 male, 3 female; 10000 mg/kg bw:  3 male, 2 female.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes, animals that died during the test and surviving animals (killed seven days after dosing) were necropsied.  Viscera of test animals were observed macroscopically.  
- Other examinations performed: clinical signs
Statistics:
LD50 calculated by a modification of the method of E.J. de Beer (no further details).  Calculation not presented.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 7 180 mg/kg bw
Based on:
test mat.
95% CL:
>= 6 570 - <= 7 830
Remarks on result:
other: equivalent to 4164 mg active acid/kg bw
Mortality:
0, 2 (females), 3 (females) and 5 deaths at 5010, 6310, 7940 and 10000 mg/kg bw, respectively. Survival times were several hours to one day.
Clinical signs:
Toxic signs included reduced appetite and activity, slight lethargy (lasting two to seven days in survivors), rapidly increasing weakness, collapse and death.
Body weight:
Surviving female rats sustained weight loss in seven days. Males recovered initial weight loss and most showed weight gain.
Gross pathology:
In animals that died there was slight liver discolouration and acute gastrointestinal inflammation. Seven days after administration the viscera of surving animals appeared normal at macroscopic examination.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study (reliability score 2) conducted prior to the adoption of OECD guidelines and GLP, the LD50 for DTPMP-H was 7180 mg/kg (previous reviewer comment: presumed equivalent to 4164 mg active acid/kg bw) in the rat.
Executive summary:

In an acute oral toxicity study (reliability score 2) conducted prior to the adoption of OECD guidelines and GLP, a single dose of DTPMP-H was administered to by oral gavage to Sprague-Dawley rats (mixed sex 5/dose). Doses of 5010, 6310, 7940 and 10000 mg/kg bw were tested. The animals were then observed for seven days, after which surviving animals were killed. All animals were examined macroscopically. There were 0, 2 (females), 3 (females) and 5 deaths at 5010, 6310, 7940 and 10000 mg/kg bw, respectively. Survival times were several hours to one day. Toxic signs included reduced appetite and activity, slight lethargy (lasting two to seven days in survivors), rapidly increasing weakness, collapse and death. Surviving female rats sustained weight loss in seven days. Males recovered initial weight loss and most showed weight gain. In animals that died there was slight liver discolouration and acute gastrointestinal inflammation. Seven days after administration the viscera of surviving animals appeared normal at macroscopic examination. The LD50 was calculated to be 7180 mg/kg bw (equivalent to 4164 mg active acid/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 164 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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Conducted prior to adoption of OECD test guidelines.
Deviations:
yes
Remarks:
Limited detail on test substance, methods and animals/conditions.
Principles of method if other than guideline:
Method: other: Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 1.8 to 2.0 kg
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: 'plastic strips'


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Constant volume or concentration used: No data



Duration of exposure:
24 hours
Doses:
3160, 5010, 7940 and 7940 mg/kg bw
No. of animals per sex per dose:
One male or female animal per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, and macroscopic examination of all animals.
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 940 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to >4605 mg active acid/kg bw
Mortality:
No deaths occurred.
Clinical signs:
Clinical symptoms included reduced appetite and activity for 1-2 days. 
Body weight:
No adverse effects reported, although the summary table shows that there was no weight change in animals five days after treatment.
Gross pathology:
No adverse findings.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and GLP, the LD50 for DTPMP-H was >7940 mg/kg bw (equivalent to >4605 mg active acid/kg bw) in the rabbit.
Executive summary:

In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and GLP, 58% w/w solution of DTPMP-H was applied to the clipped, intact skin of four New Zealand white rabbits, under an occlusive dressing, for 24 hours. Animals were then observed for 14 days, and all animals were examined macroscopically. No animals died and the LD50 was concluded to be greater than 7940 mg/kg bw (equivalent to >4605 mg active acid/kg bw). Toxic signs included reduced appetite and activity for one to two days after treatment. There were no abnormal macroscopic findings.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 605 mg/kg bw

Additional information

In the key acute oral toxicity study (Younger Laboratories, 1971) a single dose of a 58% w/w solution of DTPMP-H was administered by oral gavage to Sprague-Dawley rats (mixed sex 5/dose). Doses of 5010, 6310, 7940 and 10000 mg/kg bw were tested. The animals were then observed for seven days, after which they were examined macroscopically. There were 0, 2 (females), 3 (females) and 5 deaths at 5010, 6310, 7940 and 10000 mg/kg bw, respectively. Survival times were several hours to one day. Toxic signs included reduced appetite and activity, slight lethargy (lasting two to seven days in survivors), rapidly increasing weakness, collapse and death. Surviving female rats sustained weight loss in seven days. Males recovered initial weight loss and most showed weight gain. In animals that died there was slight liver discolouration and acute gastrointestinal inflammation. Seven days after administration the viscera of surviving animals appeared normal at macroscopic examination. The LD50 was calculated to be 7180 mg/kg bw (equivalent to 4164 mg active acid/kg bw). The study meets generally accepted scientific principles, but pre-dated GLP.

In the key acute dermal toxicity study (Younger Laboratories, 1971), 58% w/w solution of DTPMP-H was applied to the clipped, intact skin of four New Zealand white rabbits, under an occlusive dressing, for 24 hours. Animals were then observed for 14 days, and all animals were examined macroscopically. No animals died and the LD50 was concluded to be greater than 7940 mg/kg bw (equivalent to >4605 mg active acid/kg bw). Clinical signs included reduced appetite and activity for one to two days after treatment. There were no abnormal macroscopic findings. There are no inhalation data. The study meets generally accepted scientific principles, but pre-dated GLP.

Justification for classification or non-classification

Based on the available data, DTPMP-H does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.