Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

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:
The rationale to read across the data is attached in Section 13.
Reason / purpose for cross-reference:
read-across source
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Salivation. Decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair .
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
significant decrease in body weight females after parturition.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
significant decrease in body weight females after parturition.
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition.

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
Salivation was observed on the 4th day of administration and later in male and female rats at 5 mg/kg bw/day and higher. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Significant decrease in food consumption was observed at 20 mg/kg bw/day on Day 3 in male animals and on gestation day (GD) 20 in female animals.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects on days required for successful copulation, copulation index, fertility indices of males and females, implantation index, gestation length and delivery index.
Dose descriptor:
NOAEL
Effect level:
5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Effects seen at 20 mg/kg bw: death (2 females), significant decrease in food consumption, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, loss of hair and a significant decrease in body weight after parturition.
Dose descriptor:
NOAEL
Effect level:
>= 20 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no fertility effects observed
Clinical signs:
no effects observed
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
At 20 mg/kg, 18% of newborns were dead.
Body weight and weight changes:
no effects observed
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features.
The percentage of live newborns at birth was 97.7%, 98.4%, 100% and 85.4% for 0, 1, 5 and 20 mg/kg bw respectively. The number of offspring per dam was 13.2, 14, 13.5 and 12.3 for 0, 1, 5 and 20 mg/kg bw respectively.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 20 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects seen at highest test concentration.
Reproductive effects observed:
not specified

Table 1. Mating and fertility findings in the reproductive/developmental toxicity screening test of tetramethylammonium hydroxide.
============================================================
Parameter
                        Dose (mg/kg bw/day)
                          --------------------------------
                            0     1      5     20
-----------------------------------------------------------
[Male]
No. of animals mated
       10    10     10     11
No. of animals that copulated
                           10    10     10     10
No. of animals that produced pregnant female
                           10    10     10     10
-----------------------------------------------------------
[Female]
No. of animals mated
       10    10     10     10
No. of animals that copulated
                           10    10     10     10
No. of pregnant animals
    10    10     10     10
-----------------------------------------------------------
Duration of mating(days required for successful copulation)
 Mean                     3.0   2.7    3.2    4.7
 S.D.                    1.49   1.42   1.03   5.44
============================================================

Table 2. Postnatal outcomes in the reproductive/developmental toxicity screening test of tetramethylammonium hydroxide.
============================================================
Parameter
                    Dose (mg/kg bw/day)
                     ----------------------------------
                      0        1         5       20
-----------------------------------------------------------
[Dam]
No. of dams
          10       10        10         9   
No. of dams delivered live newborns
                     10        9        10         8
Duration of pregnancy(day)
 Mean              22.0      22.0     21.8      22.3
 S.D.              0.00      0.50     0.42      0.46
No. of implantation sites 1)
                 141(14.1) 147(14.7) 148(14.8) 123(13.7)
-----------------------------------------------------------
[Newborns]
No. of newborns
  
 Total 2)       132(13.2) 126(14.0) 135(13.5)  98(12.3)
 Male            61        65        71        45
 Female          71        61        64        52
No. of stillborns
  0         0         0         1(Male)
Sex ratio of live newborns at birth (male/female)
                   61/71     65/61     71/64     44/52
No. of deads
         3         2         0        14
No. of live newborns on PND 4
 Total 3)       129(97.7) 124(98.4) 135(100)  82(85.4)
 Male 3)         58(95.1)  64(98.5)  71(100)   37(84.1)
 Female 3)       71(100)   60(98.4)  64(100)   45(86.5)
============================================================
1) The value in parentheses is the number of implantation sites per dam.
2) The value in parentheses is the number of total newborns per dam delivered live newborns.
3) The value in parentheses is percentage of live newborns at birth.

Table 3. External findings on newborns in the reproductive/developmental toxicity screening test of tetramethylammonium hydroxide.
============================================================
Parameter
                        Dose(mg/kg bw/day)
                      ------------------------------------
                           0      1      5      20
-----------------------------------------------------------
No. of dams
               10      9     10       8
-----------------------------------------------------------
[PND 0]
No. of newborns examined
 132    126    135      82
No. of newborns with abnormalities
                           0      0      0       0
-----------------------------------------------------------
[PND 4]
No. of newborns examined
 129    124    135      82
No. of newborns with abnormalities
                           0      0      0       0
============================================================

Conclusions:
In a reproductive/developmental toxicity screening test in rats according to OECD guideline 421 and GLP principles, the NOAEL for parental toxicity was found to be 5 mg/kg bw. Since no effects were seen on fertility and development, the NOAELs for these endpoint were found to be >= 20 mg/kg bw. The result is read across to TEAH.
Executive summary:

A reproductive/developmental toxicity screening test was performed with rats according to OECD guideline 421 and GLP principles. TMAH was dosed by oral gavage at 0, 1, 5 and 20 mg/kg bw. A significant decrease in food consumption was observed at 20 mg/kg bw/day on Day 3 in male animals and on gestation day (GD) 20 in female animals. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter, and a significant decrease in body weight on days 0 and 4 after parturition (PND 0 and 4). One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition. Tetramethylammonium hydroxide showed no effect on any of the following parental reproductive parameters; days required for successful copulation, copulation index, fertility indices of males and females, implantation index, gestation length and delivery index. There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features.

Based on these observations, the NOAEL for parental toxicity was found to be 5 mg/kg bw/day and for reproduction/developmental toxicity >= 20 mg/kg bw/day in rats. The result is read across to TEAH.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
Study conducted following OECD guideline 421 and GLP principles. Study is reliable (Klimisch score 2). However, as it was conducted with a substance analogue, the maximum Klimisch score is 2.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A reproductive/developmental toxicity screening test with substance analogue TMAH was performed with rats according to OECD guideline 421 and GLP principles. TMAH was dosed by oral gavage at 0, 1, 5 and 20 mg/kg bw.A significant decrease in food consumption was observed at 20 mg/kg bw/day on Day 3 in male animals and on gestation day (GD) 20 in female animals. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter, and a significant decrease in body weight on days 0 and 4 after parturition (PND 0 and 4). One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition.Tetramethylammonium hydroxide showed no effect on any of the following parental reproductive parameters; days required for successful copulation, copulation index, fertility indices of males and females, implantation index, gestation length and delivery index.There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features.

Based on these observations, the NOAEL for parental toxicity was found to be 5 mg TMAH/kg bw/day and for reproduction/developmental toxicity >= 20 mg TMAH/kg bw/day in rats. According to the rationale attached in section 13, these data can be read across to TEAH.


Short description of key information:
In a reproductive/developmental toxicity screening test with substance analogue TMAH in rats performed according to OECD guideline 421 and GLP principles, the NOAEL for parental toxicity was found to be 5 mg TMAH/kg bw. Since no effects were seen on fertility and development, the NOAELs for these endpoint were found to be >= 20 mg TMAH /kg bw. According to the rationale attached in section 13, these data can be read across to TEAH.

Justification for selection of Effect on fertility via oral route:
One study performed with substance analogue TMAH is available.

Effects on developmental toxicity

Description of key information
In a reproductive/developmental toxicity screening test in rats with substance analogue TMAH, the NOAEL for parental toxicity was found to be 5 mg/kg bw/d and for developmental toxicity >=20 mg/kg bw/d. According to the rationale attached in section 13, these data can be read across to TEAH. 
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Remarks:
Screening study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Maternal toxic effects:yes. Remark: Two females died, clinical effects were seen and decrease in weight gain.

Details on maternal toxic effects:
One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition.

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
Salivation was observed on the 4th day of administration and later at 5 mg/kg bw/day and higher. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Significant decrease in food consumption was observed at 20 mg/kg bw/day on gestation day (GD) 20 in female animals.
.
Dose descriptor:
NOAEL
Effect level:
5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes. Remark: Lowered number of live newborns at birth

Details on embryotoxic / teratogenic effects:
There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features.
The percentage of live newborns at birth was 97.7%, 98.4%, 100% and 85.4% for 0, 1, 5 and 20 mg/kg bw respectively. The number of offspring per dam was 13.2, 14, 13.5 and 12.3 for 0, 1, 5 and 20 mg/kg bw respectively.
Dose descriptor:
NOAEL
Effect level:
>= 20 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: developmental toxicity
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
In a reproductive/developmental toxicity screening test in rats according to OECD guideline 421 and GLP principles, the NOAEL for parents was found to be 5 mg TMAH/kg bw and the developmental NOAEL was found to be >= 20mg TMAH/kg bw. The result is read across to TEAH.
Executive summary:

A reproductive/developmental toxicity screening test was performed with rats according to OECD guideline 421 and GLP principles. TMAH was dosed by oral gavage at 0, 1, 5 and 20 mg/kg bw. A significant decrease in food consumption was observed at 20 mg/kg bw/day on Day 3 in male animals and on gestation day (GD) 20 in female animals. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter, and a significant decrease in body weight on days 0 and 4 after parturition (PND 0 and 4). One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition.Tetramethylammonium hydroxide showed no effect on any of the following parental reproductive parameters; days required for successful copulation, copulation index, fertility indices of males and females, implantation index, gestation length and delivery index.There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features. However, the percentage of live newborns at birth was 97.7%, 98.4%, 100% and 85.4% for 0, 1, 5 and 20 mg/kg bw respectively.

Based on these observations, the NOAEL for parental toxicity was found to be 5 mg TMAH/kg bw/day in rats. No effects on development were seen at the highest test concentration, therefore the developmental NOAEL for TMAH was considered to be >= 20mg/kg bw. The result is read across to TEAH.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
Study conducted following OECD guideline 421 and GLP principles. However, as it was conducted with a substance analogue, the maximum Klimisch score is 2.
Additional information

A reproductive/developmental toxicity screening test with substance analogue TMAH was performed with rats according to OECD guideline 421 and GLP principles. TMAH was dosed by oral gavage at 0, 1, 5 and 20 mg/kg bw.A significant decrease in food consumption was observed at 20 mg/kg bw/day on Day 3 in male animals and on gestation day (GD) 20 in female animals. In the female animals at 20 mg/kg bw/day, a decrease in locomotor activity, incomplete eyelid opening or eyelid closure, and loss of hair were observed on GD 21 and thereafter, and a significant decrease in body weight on days 0 and 4 after parturition (PND 0 and 4). One female rat at 20 mg/kg bw/day died on GD 22 and another one on GD 23 during parturition.Tetramethylammonium hydroxide showed no effect on any of the following parental reproductive parameters; days required for successful copulation, copulation index, fertility indices of males and females, implantation index, gestation length and delivery index.There was no effect of tetramethylammonium hydroxide on either the numbers of total newborns, sex ratio. No compound-related abnormality was observed either in external features. However, the percentage of live newborns at birth was 97.7%, 98.4%, 100% and 85.4% for 0, 1, 5 and 20 mg/kg bw respectively.

Based on these observations, the NOAEL for parental toxicity was found to be 5 mg/kg bw/day and for developmental toxicity was >=20 mg/kg bw/d in rats. According to the rationale attached in section 13, these data can be read across to TEAH.

Justification for selection of Effect on developmental toxicity: via oral route:
One study available, performed with substance analogue TMAH.

Justification for classification or non-classification

Based on the available data, TEAH (or a 35% aqueous solution of TEAH) is not classified for reproduction toxicity according to CLP Regulation (EC) No. 1272/2008.

Additional information