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EC number: 200-882-9 | CAS number: 75-59-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study conducted following OECD guideline 421 and GLP principles. However, only limited data were available for review.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: not reported
- Age at study initiation: (P) 9 wks; (F1) 4 days
No further details provided. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details reported.
- Details on mating procedure:
- No details reported.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Male: 14 days before mating to the day before scheduled death through mating (total 32 days).
Female: 14 days before mating to 3 days after delivery through mating and gestation periods. - Frequency of treatment:
- daily
- Details on study schedule:
- No details reported
- Remarks:
- Doses / Concentrations:
0, 1, 5, 20 mg/kg bw
Basis:
actual ingested - No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- For mating, one male to one female mating was used. A female rat was placed together with a male rat until copulation occurred. When no copulation was observed, the female animal was mated with another male animal of the same dose group for additional 14 days. Day 0 of gestation (GD 0) was defined as the day a vaginal plug or sperm was found.
- Positive control:
- No
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes, twice daily
BODY WEIGHT: Yes, males were weighed on Day 1 and 3 of dosing, and weekly thereafter. Females were weighed on Day 1, 3 and 7 of dosing, weekly thereafter until delivery, and PND 0 and 4. - Litter observations:
- Clinical signs and body weights of the live pups were recorded.
- Postmortem examinations (parental animals):
- Autopsy at end of experiment.
- Postmortem examinations (offspring):
- Autopsy at end of experiment.
- Statistics:
- Statistical analysis : Bartlett's test, one-way analysis of variance, Dunnett's test, Kruskal-wallis test, chi-square test
- 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
- 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
- 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
- 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.
- 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.
Reference
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.
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.
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
============================================================
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 = 1).
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 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.Short description of key information:
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.
Justification for selection of Effect on fertility via oral route:
One study available.
Effects on developmental toxicity
Description of key information
In a reproductive/developmental toxicity screening test in rats, the NOAEL for parental toxicity was found to be 5 mg/kg bw/d and for developmental toxicity >=20 mg/kg bw/d.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study conducted following OECD guideline 421 and GLP principles. However, only limited data are available for review.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 421OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: not reported
- Age at study initiation: (P) 9 wks; (F1) 4 days
No further details provided. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on mating procedure:
- One male to one female mating was used. A female rat was placed together with a male rat until copulation occurred. When no copulation was observed, the female animal was mated with another male animal of the same dose group for additional 14 days.
- Duration of treatment / exposure:
- Male: 14 days before mating to the day before scheduled death through mating (total 32 days).
Female: 14 days before mating to 3 days after delivery through mating and gestation periods. - Frequency of treatment:
- Daily
- Duration of test:
- Females and pups were sacrificed at 4 days after birth.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes, twice daily
BODY WEIGHT: Yes, females were weighed on Day 1, 3 and 7 of dosing, weekly thereafter until delivery, and post natal day 0 and 4. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: No
- Fetal examinations:
- - External examinations and gross pathology: Yes, all per litter
- Statistics:
- Statistical analysis : Bartlett's test, one-way analysis of variance, Dunnett's test, Kruskal-wallis test, chi-square test.
- 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/kg bw and the developmental NOAEL was found to be >= 20mg/kg bw.
- 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/kg bw/day in rats. No effects on development were seen at the highest test concentration, therefore the developmental NOAEL was considered to be >= 20mg/kg bw.
Reference
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. Study is reliable (klimisch score = 1).
Additional information
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/kg bw/day and for developmental toxicity was >=20 mg/kg bw/d in rats.Justification for selection of Effect on developmental toxicity: via oral route:
One study available.
Justification for classification or non-classification
Based on the available data, TMAH is not classified for reproduction toxicity according to CLP Regulation (EC) No. 1272/2008.
Additional information
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