Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

No data are available for BHMT-H. However, information is available for other members of the super-category: DTPMP acid, (CAS number 15827-60-8), DTPMP-xNa (CAS number 22042-96-2), EDTMP acid (CAS number 1429-50-1), HMDTMP acid (CAS number 23605-74-5) and HMDTMP-xNa (CAS number 56744-47-9). Read-across between acids and salts is considered scientifically justified as the counter ions potassium and sodium are not significant in genotoxicity and have been assessed in depth in the public literature. Read-across from categories DTPMP, EDTMP and HMDTMP to the registered substance, BHMT-H, is considered justified as all these categories and BHMT-H are members of the same super-category. A more detailed justification of read-across is included in the CSR at the beginning of chapter 5; more information on the super-category is presented in the CSR section 1.

 

DTPMP-xNa has been tested in a reliable bacterial mutagenicity assay, conducted according to OECD guideline 471 and in compliance with GLP. The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2. No increase in the number of revertants was observed in Salmonella typhimurium TA98, TA100, TA 1535, TA 1538 and E. coli WP2 uvrA with or without metabolic activation, in either the initial or the repeat assay. It is concluded that the substance is negative for mutagenicity to bacteria under the conditions of the test (Machigaki (2001)).

 

HMDTMP-xNa has been tested according to a protocol that is similar to OECD 471, using Salmonella typhimurium strains TA 98 and TA 100. No increase in the number of revertants was observed at any concentration with and without metabolic activation. Appropriate untreated, solvent and positive controls were included and gave expected results (Manley A (1981)).

HMDTMP-acid has been tested according to a protocol that is similar to OECD 471. Full details are not included in the summary report available. No evidence of mutagenicity was observed at any concentration in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 with and without metabolic activation. Appropriate solvent and positive controls were included and gave expected results (Flowers L (1976)).

 

DTPMP-xNa has been tested in a reliable study conducted according a protocol that is equivalent to OECD guideline 473 and under GLP. The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2. A dose related increase in the number of cells with aberrations was observed after 48 hours treatment in an in vitro chromosome aberration assay. It is concluded that the substance is positive for induction of chromosome aberrations in Chinese hamster lung cells under the conditions of the test (Nakamura, (2001)).

 

EDTMP-H has been tested according to protocol that is similar to OECD 473. No test substance-induced increase in the incidence of chromosome aberrations in Chinese hamster ovary cells was observed with or without metabolic activation using either Lot A or Lot B. Appropriate solvent and positive controls were included and gave expected results (Li A. P., Myers C. A. (1986)).

 

DTPMP-xNa has been tested in a reliable study, conducted according to OECD guideline 476, and in compliance with GLP. No genotoxicity was seen in an in vitro mouse lymphoma L5178Y cell mutagenicity assay in the presence or absence of S9. However, the highest concentration selected for testing was below the maximum required by the guideline (Clay, (1997)).

 

HMDTMP-H has been tested according to a protocol that is similar to OECD 476. No increase in the mutant frequency was observed at any concentration up to cytotoxic concentrations, with and without metabolic activation. Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the substance is negative for mutagenicity to L5178Y mouse lymphoma cells under the conditions of the test. (Matheson D.W. (1978)).

 

DTPMP-H has been tested in a reliable study, conducted using a protocol similar to OECD guideline 475, and in compliance with GLP. No evidence of clastogenicity was seen in rat bone marrow following a single oral gavage administration at doses up to the maximum tolerated dose of 1970 mg active acid/kg bw (Farrow, (1983)).


Justification for selection of genetic toxicity endpoint
The selected studies were the more reliable and/or most recent of the available data for all the surrogate substances. They were conducted according to appropriate OECD guidelines, or protocols similar to OECD guidelines, and under GLP.

Short description of key information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): Read-across from DTPMP-xNa: negative with and without activation in Salmonella typhimurium TA98, TA100, TA 1535, TA 1538 and E. coli WP2 uvrA (OECD TG 471) (Machigaki (2001)).
Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from HMDTMP-xNa: negative with and without activation in Salmonella typhimurium strains TA98 and TA100 (similar to OECD 471) (Manley A (1981)).
Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from HMDTMP-H: negative with and without activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 (similar to OECD 471) (Flowers L (1976)).
Cytogenicity in mammalian cells: Read-across from DTPMP-xNa: positive in Chinese hamster lung IU cells (OECD TG 473) (Nakamura, (2001)).
Cytogenicity in mammalian cells: read-across from EDTMP-H: negative with and without metabolic activation in CHO cells (similar to OECD TG 473) (Li A. P., Myers C. A. (1986)).
Mutagenicity in mammalian cells: Read-across from DTPMP-xNa: negative in L5278Y cells (similar to OECD TG 476) (Clay, 1997).
Mutagenicity in mammalian cells: read-across from HMDTMP-H: negative with and without metabolic activation in L5178Y mouse lymphoma cells (similar to OECD TG 476) (Matheson D.W. (1978)).

In vivo:
Bone marrow chromosome study in rats (oral gavage administration): Read-across from DTPMP-H: Negative (similar to OECD TG 475) (Farrow, (1983)).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo genotoxicity data for the closely related substances DTPMP acid, DTPMP-xNa, EDTMP acid, HMDTMP acid, HMDTMP-xNa and HMDTMP-xK, BHMT-H is not classified according to Regulation 1272/2008/EC.