Registration Dossier

Administrative data

Description of key information

There are no acute toxicity data for HMDTMP (4-7Na). Therefore, data have been read-across from HMDTMP sodium salt (CAS 56744-47-9). See attachment to Section 13 for justification of read-across within HMDTMP Category.

 

The key acute oral toxicity study for HMDTMP-xNa (CAS 56744-47-9), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an oral LD50 value of ≥15 ml/kg in rat. The equivalent LD50 value for the active acid based on this value is ≥3.75 ml/kg, which is estimated to be equal to 4875 mg/kg active acid (Safepharm Laboratories, 1982).

 

The key acute dermal toxicity study for HMDTMP-xNa (CAS 56744-47-9), conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of ≥10 ml/kg in rat. The equivalent LD50 value for the active acid based on this value is ≥2.5 ml/kg. The estimated LD50 for the active acid is therefore ≥3250 mg/kg (Safepharm Laboratories, 1982).

There are no acute inhalation toxicity data available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attachment to Section 13 for justification of read across.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 15 mL/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 4 875 mg/kg bw
Based on:
act. ingr.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 875 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:
3.8.1982 - 17.8.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A. Tuck & Sons Ltd., Battlesbridge, Essex
- Age at study initiation: ca. 6-8 weeks
- Weight at study initiation: 235-260g (males), 212-231g (females)
- Housing: The rats were randomly allocated to cages within treatment groups. They were housed individually during the 24 hour exposure period and in groups of five for the remainder of the study in polypropylene cages with sawdust bedding.
- Diet: standard laboratory rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the trunk
- Type of wrap if used: The trunk of the rat was encircled with a strip of elastic adhesive bandage 7.5cm wide and 25-30cm long, backed with aluminium foil. The bandage was tightened sufficently to prevent the animal from wriggling free and wrapped round to form a double layer.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin and surrounding hair were sponged thoroughly with warm water and rinsed and dried using absorbent paper, after the removal of the bandage and foil.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10ml/kg
- Concentration (if solution): undiluted


Duration of exposure:
24 hours
Doses:
10ml/kg
No. of animals per sex per dose:
5M, 5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed at 0.5, 1, 2, 3, 4 and 5 hours following dosing. On subsequent days animals were observed at least once. Mortalities and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The macroscopic appearance of abnormal organs were recorded.
Statistics:
Using the mortality data, an assessment of the acute percutaneous median lethal dose of the test material was made.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 10 mL/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 3 250 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities occurred during the fourteen day observation period.
Clinical signs:
No signs of reaction to treatment were observed in any animal throughout the observation period.
Body weight:
Bodyweight gains appeared to be within normal limits throughout the two week observation period.
Gross pathology:
Autopsy of animals killed on day 14 did not reveal any macroscopic abnormalities.
Other findings:
None reported.

LD50 >2.5 ml/kg (a.i.)

specific gravity 1.3

LD50 >3250 mg/kg

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of >10 ml/kg in rat was reported in a reliable study conducted according to an appropriate protocol and in compliance with GLP. The equivalent LD50 value for the active acid based on this value is >2.5 ml/kg. The estimated LD50 for the active acid is therefore >3250 mg/kg. The result is read across from HMDTMP sodium salt (CAS 56744-47-9).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 250 mg/kg bw

Additional information

There are no acute toxicity data for HMDTMP (4-7Na). Therefore, data have been read-across from HMDTMP-xNa(CAS 56744-47-9). See attachment to Section 13 for justification of read-across within HMDTMP Category.

 

The key acute oral toxicity study for HMDTMP-xNa (CAS 56744-47-9), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an oral LD50 value of ≥15 ml/kg in rats. The equivalent LD50 value for the active acid based on this value is ≥3.75 ml/kg, which is estimated to be equal to 4875 mg/kg active acid (Safepharm Laboratories, 1982). Following single oral gavage administration of 15 ml/kg undiluted HMDTMP-xNa (CAS 56744-47-9) to 5 male and 5 female rats, the animals were observed for clinical signs of toxicity at 0.5, 1, 2, 3, 4 and 5 hours post-dosing; thereafter, the animals were observed at least once a day for the remaining 14-day study period. Mortalities and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on days 0, 7 and 14. At the end of the 14-day study period, the animals were sacrificed and the organ weights and macroscopic appearance of the abdominal organs were recorded during necropsy. No mortalities occurred during the 14-day observation period at a dose level of 15ml/kg test substance, which equates to 3.75 ml/kg active acid. Signs of reaction to treatment observed shortly after dosing in all rats consisted of piloerection, abnormal body carriage (hunched posture), lethargy and decreased respiratory rate. Recovery of all rats, as judged by external appearance and behaviour was complete by day 4. Bodyweight gains in all rats, appeared to be within normal limits throughout the two-week observation period. No macroscopic abnormalities were seen in any during necropsy.

 

The key acute dermal toxicity study for HMDTMP-xNa(CAS 56744-47-9), conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of ≥10 ml/kg in rats. The equivalent LD50 value for the active acid based on this value is ≥2.5 ml/kg. The estimated LD50 for the active acid is therefore ≥3250 mg/kg (Safepharm Laboratories, 1982). Following a 24-hour semioccluded topical application of 10 ml/kg undiluted HMDTMP-xNa (CAS 56744-47-9) onto the skin of 5 male and 5 female rats, the animals were observed for clinical signs of toxicity at 0.5, 1, 2, 3, 4 and 5 hours post-dosing; thereafter, the animals were observed at least once a day for the remaining 14-day study period. Mortalities and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on days 0, 7 and 14. At the end of the 14-day study period, the animals were sacrificed and the organ weights and macroscopic appearance of the abdominal organs were recorded during necropsy. No mortalities occurred during the 14-day observation period. No signs of reaction to treatment were observed in any animal throughout the observation period. Recovery of all rats, as judged by external appearance and behaviour was complete by day 4. Bodyweight gains in all rats, appeared to be within normal limits throughout the two-week observation period. No macroscopic abnormalities were seen in any during necropsy.

Justification for classification or non-classification

Based on the available information, no classification is required for HMDTMP (4-7Na) for acute toxicity according to Regulation (EC) No 1272/2008.