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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL (reproductive toxicity) = 125 mg/kg bw/d; OECD TG 421: at 500 mg/kg/day,: increase in post implantation loss, statistically significantly lower rate of live born pups; read-across from DODMAC

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: quaternary ammonium and saturated or unsaturated alkyl chains with comparable length (corresponding to scenario 2 of the read-across assessment framework)

The read-across hypothesis is based on structural similarity of target and source substances. Based on available experimental data, including key physicochemical properties and data from acute toxicity, irritation, sensitization (human) and genotoxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all substances.

Therefore, read-across from the existing ecotoxicity, environmental fate and toxicity studies conducted with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A justification for read-across is attached to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See justification for read-across attached to IUCLID section 13.

3. ANALOGUE APPROACH JUSTIFICATION
See justification for read-across attached to IUCLID section 13.

4. DATA MATRIX
See justification for read-across attached to IUCLID section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Species:
rat
Sex:
male/female
Route of administration:
oral: gavage
Frequency of treatment:
once daily
Description (incidence and severity):
Test substance intake: not applicable for gavage administration
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Critical effects observed:
no
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
125 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: At the higher dose-level of 500 mg/kg bw (which is also the highest dose of the study), the live birth index was statistically decreased compared to controls (83% versus 94%).
Reproductive effects observed:
no
Conclusions:
Based on the findings of this study, it was concluded that the No-observed-adverse-effect level (NOAEL) regarding reproductive toxicity was 125 mg/kg bw/day.
Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
125 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No experimental data on reproductive toxicity are available for the target substance Di-C12-18 alkyl-dimethyl ammonium chloride. A Reproduction / Developmental Toxicity Screening Test is available for the closely related source substance DODMAC. A justification for read-across is attached to IUCLID section 13.

 

The objective of this study was to evaluate the potential reproductive/developmental toxicity of DODMAC (96.8% active) according to a GLP conform Reproduction/Developmental Toxicity Screening Test (OECD Guideline 421).

Groups of 10 rats (CRL:CD (SD) BR) per sex were treated with dosages of 0, 62.5, 125, and 500 mg/kg bw/day by gavage (administration volume 10 ml/kg bw/day) using corn oil as a vehicle for the control group. Males were treated daily from two weeks before mating, during mating and until a dosing period of a total of 28 days had been completed. Females were treated daily from two weeks before mating until the 4 th day of lactation. Subsequently these females were sacrificed with their pups.

At daily doses of 500 mg/kg bw one male and one female died after 12 and 10 treatments respectively. Clinical observations revealed dyspnea, soft stools in all females and almost all males. Half of the females also showed slight to moderate dilation of the abdomen. Body weight loss of about 14 to 15 g was observed in both sexes during the first week of treatment. Further, statistically significantly lower mean daily food consumption was observed in the males during the premating period and in the dams during the first week of pregnancy. Statistically significantly lower mean dam body weights were observed after 14 and 20 days of gestation and at the day of birth after delivery.

No toxicologically relevant effects were observed at dosages of 125 and 62.5 mg/kg bw/day.

At sacrifice of the parental animals no significant differences were found in the organ weights of uterus, ovaries, testes and epididymides. Histopathology of testes, epididymides and of the ovaries of the animals of the 500 mg/kg dose groups did not show any compound related changes. No substance related changes were reported for the evaluation of testicular stages of spermatogenesis performed in the PAS-hematoxylin stained sections.

At the dosages of 62.5 and 125 mg/kg/day all of the 10 paired females revealed to be sperm positive after mating, all revealed to be pregnant and all delivered live litters. The numbers of corpora lutea had not been evaluated during this study.

At 500 mg/kg/day, from the 9 paired females 7 revealed to be sperm positive (77 %) after mating, 6 out of 9 (67 %) revealed to be pregnant, and 5 out of 6 (83 %) delivered live litters. One animal revealed to have fully resorbed. Mean pre-coital time was longer in this group (about 6.1 days) when compared to the controls and the lower dosage groups (1.5 to 2.1 days).

After birth, for the animals treated with 62.5 or 125 mg/kg/day there were no substance related biological differences in their pregnancy outcome in comparison to the control group. At 500 mg/kg/day, the percentage of post implantation losses was increased by 19% per litter in comparison to about 6% per litter in the controls and in the lower treatment groups, thus resulting in a statistically significantly lower rate of live borns of 83% in comparison to 94% in the controls and in the lower treatment groups. Viability index on postnatal day 4 was in the range of the controls and the lower treatment groups.

For all dose groups under investigation no statistically significant differences were found for the body weights of male and female pups at birth and on postnatal day 4. External abnormalities have not been reported.

Based on the findings of this study, it was concluded that the No-observed-adverse-effect level (NOAEL) regarding reproductive toxicity was 125 mg/kg bw/day.

There are no data gaps for effects on fertility. No human data are available. However, there is no reason to believe that these results from rat would not be applicable to humans.

Effects on developmental toxicity

Description of key information

NOAEL (maternal toxicity, development/teratogenicity) >/= 500 mg/kg bw/d; OECD TG 414, rat; read-across from DTDMAC

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: quaternary ammonium and saturated or unsaturated alkyl chains with comparable length (corresponding to scenario 2 of the read-across assessment framework)

The read-across hypothesis is based on structural similarity of target and source substances. Based on available experimental data, including key physicochemical properties and data from acute toxicity, irritation, sensitization (human) and genotoxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all substances.

Therefore, read-across from the existing ecotoxicity, environmental fate and toxicity studies conducted with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A justification for read-across is attached to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See justification for read-across attached to IUCLID section 13.

3. ANALOGUE APPROACH JUSTIFICATION
See justification for read-across attached to IUCLID section 13.

4. DATA MATRIX
See justification for read-across attached to IUCLID section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Depressed body weight gains and lower feed consumption during gestation in group having received the test compound in the diet.
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No differences considered to be related to the administration of the test substance were noted in fetal size and sex, variations in degree of ossification or malformations.
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: no effects at highest dose level
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
Based on the available results, the target substance is not considered to be a developmental toxicant.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No experimental data on developmental toxicity are available for the target substance Di-C12-18 alkyl-dimethyl ammonium chloride. Though not an information requirement at this tonnage level, data from a closely related source substance (DTDMAC) for prenatal developmental toxicity are presented. A justification for read-across is attached to IUCLID section 13.

 

Ditallowdimethylammonium chloride (DTDMAC) was investigated for developmental toxicity in the rat. 25 female rats per group were administered the test substance either by oral gavage at dose levels of 100 and 500 mg active ingredient per kg body weight per day (vehicle was 15% isopropanol) or in the diet at a dose level of 0.65% active ingredient beginning on day 6 of gestation. Two control groups were run concurrently. One received the gavage vehicle and the other received control feed only.

Ten rats per group were sacrificed after the day 13 treatment and 15 rats per group were treated through day 18 and sacrificed on day 21 of gestation. Body weights were taken on days 0, 6, 9, 12, 15, 18 and 21 of gestation. Food consumption was evaluated for days 12 and 18 of gestation. Clinical observations were made daily for signs of pharmacologic or toxicologic effect and mortality. Gross necropsies were conducted on all surviving rats, moribund rats and rats that died spontaneously. At necropsy, for rats sacrificed on day 13 of gestation, the uterus (number and location for each horn of resoptions, embryos and implantation sites) and ovaries (number of corpora lutea of pregnancy per ovary) were observed. At necropsy for rats sacrificed on day 21 of gestation, the uterus (number and location for each horn of live fetuses, dead fetuses, early and late resorptions and impantation sites) and ovaries ( number of corpora lutea of pregnancy per ovary) were observed. The necropsy for all maternal rats also included observations for obvious abnormalities and the following tissues were examined: heart, lung, stomach, liver, pancreas, spleen, mesenteric lymph nodes, jejunum, kidney, adrenal, bladder and ovary.

With regard to maternal data, no adverse effects attributable to DTDMAC administration were noted in comparison of pregnancy and mortality rates. Depressed body weight gains during gestation were noted in the group that received the test substance in the diet together with less food consumption values compared to the group that received control feed. Early deliveries and abortions, necropsy findings, and reproduction data were considered not to be affected by treatment with the test substance. An increase in resorptions was observed for the 100 mg/kg/day gavage group compared to the isopropanol control group (7.1% vs 2.1%). This difference was not considered a treatment-related effect due to the lack of dose response and a low value for the control group compared to historical data from the laboratory.

With regard to fetal data, no differences considered to be related to the administration of DTDMAC were noted in fetal size and sex, variations in degree of ossification or malformations.

Based on the results of this study, the NOAEL for maternal toxicity was considered to be greater 500 mg/kg body weight per day by gavage. No NOAEL for maternal toxicity was established for dietary treatment because of the slight effects on body weight gain. With regard to developmental toxicity the NOAEL was established to be greater 500 mg/kg body weight per day by gavage and greater 508 mg/kg body weight per day via the diet.

There are no data gaps for developmental toxicity. No human data are available. However, there is no reason to believe that these results from rat would not be applicable to humans.

Justification for classification or non-classification

Based on the available data, the target substance Di-C12-18 alkyl-dimethyl ammonium chloride does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to reproductive or developmental toxicity.

Additional information