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Administrative data

Description of key information

The key data are read across from HMDTMP sodium salt (CAS 56744-47-9). The key study for acute oral toxicity reports an oral LD50 value of >15 ml/kg in rat, 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 >3.75 ml/kg, which is estimated to be equal to 4875 mg/kg active acid (Safepharm 1982).

The key study for acute dermal toxicity reports an LD50 value of >10 ml/kg in rat, 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 (Safepharm 1982). There is no data available for acute inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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 justification for read-across between HMDTMP category members in the attached file.
Reason / purpose:
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:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4.8.1982-18.8.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
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: A. Tuck and Sons Ltd., Battlesbridge, Essex
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: 104-118g (males), 86-108g (females)
- Fasting period before study: overnight and up to ca. 2 hours after dosing
- Housing: The rats were randomly allocated to cages within treatment groups. They were housed in groups of five in polypropylene cages with sawdust bedding.
- Diet: standard laboratory diet, ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): Not controlled, but remained within a range of 65-75%RH
- Air changes (per hr): ca. 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: 15ml/kg

Doses:
15 ml/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: Animals were observed 0.5, 1, 2, 3, 4 and 5 hours following dosing. On subsequent days the 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 was recorded.
Statistics:
An assessment of the acute oral median lethal dose of the test material was made.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 mL/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 875 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities occurred during the fourteen day observation period at a dose level of 15ml/kg test substance, which equates to 3.75 ml/kg active acid.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all rats consisted of pilo-erection, 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.
Body weight:
Bodyweight gains of all rats, appeared to be within normal limits throughout the two week observation period.
Gross pathology:
No macroscopic abnormalities were seen in any animal killed at day 14.
Other findings:
None reported.

LD50 >3.75 ml/kg (a.i.)

specific gravity 1.3

LD50 >4875 mg/kg

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of >15 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 >3.75 ml/kg, which is estimated to be equal to 4875 mg/kg active acid. The result is a read across from HMDTMP sodium salt (CAS 56744-47-9
).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
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

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See justification for read-across between HMDTMP category members in the attached file.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 3 250 mg/kg bw
Based on:
act. ingr.
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:
OECD Guideline 402 (Acute Dermal Toxicity)
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: 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 a read across from HMDTMP sodium salt (CAS 56744-47-9).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 250 mg/kg bw

Additional information

No data was available on the acute toxicity of HMDTMP-xK. The key data was therefore read across from the structurally analogous HMDTMP sodium salt (CAS 56744-47-9).

The studies selected as key were the only available data for acute toxicity for the HMDTMP-xNa salt. They were recent and reliable and therefore suitable for use as key studies.

In the acute oral toxicity study signs of reaction to treatment observed shortly after dosing in all rats consisted of pilo-erection, 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.

The inhalation endpoint is waived, since reliable data is available for the acute oral and dermal endpoints.


Justification for classification or non-classification

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