Tripropylamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study; no data regarding GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

yes

Qualifier:

according to guideline

Guideline:

other: OPPTS 870-3650

Principles of method if other than guideline:

No data on detailed clinical observation, sensory reactivity to stimuli, assessment of grip strength, and motor activity

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

-Age: 9 week old

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

no details given

Details on mating procedure:

- M/F ratio per cage: 2
- Length of cohabitation: 2 weeks
- Proof of pregnancy: [vaginal plug and sperm in vaginal smear]

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

42 days; Females: 2 weeks prior to breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).

Frequency of treatment:

Once daily

Details on study schedule:

Not applicable

Remarks:

Doses / Concentrations:
0, 8, 40, 200 mg/kg/day (in water)
Basis:
no data

No. of animals per sex per dose:

13/sex/dose group

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale:
- Rationale for animal assignment (if not random):
- Other:

Positive control:

no

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: General condition was observed at least once a day during breeding and at least twice a day before and after dosing over the administration period.


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: Body weights for males were determined on days 1, 7, 14, 21, 28, 35, 42 and on the day of necropsy. Body weights were determined for all females on days 1, 7, 14. Females who took time before mating were weighed on days 35 and 42. Females who copulated were weighed on pregnancy days 0, 7, 14 and 20. Females who delivered were weighed on nursing days 0, 4, and on the day of necropsy. Females who copulated but did not deliver were weighed on the equivalent of pregnancy day 25 (day of necropsy).

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):

Food consumption was measured on days 1, 7, 13, 29, 35 and 41 for males, and on days 1, 7, and 13 for all females. Females with unconfirmed copulation were measured for food consumption on days 29, 35 and 41.

OTHER:
- Urinalysis was conducted on 5 rats/sex/dose level at week 6.
- Hematology and clinical chemistry: Males prior to necropsy and on the  following day after day 42 administration; Females prior to necropsy:  females who delivered-following nursing day 4, females who mated but did  not deliver-equivalent of pregnancy day 25, and females who did not mate-  following day 54 of administration

Oestrous cyclicity (parental animals):

 Estrous cycle was observed from the vaginal smear and  the mean number of days of mating season was calculated..

Sperm parameters (parental animals):

no data

Litter observations:

-Number of delivered pups:  The number of delivered pups (live pups +  stillborns) was counted on nursing day 0, and the delivery rate ((number  of delivered pups/number of implantation traces) x 100) and the live  birth rate ((number of delivered live pups/number of implantation traces)  x 100) were calculated. With the delivered pups, external malformation  and the sex were checked and the sex ratio ((number of male live  pups/number of female live pups) x 100) was calculated.
-Number of dead pups: The number of dead pups was checked daily, and the  birth rate ((number of delivered live pups/number of delivered pups) x  100) and the viable rate of new-born pups on day 4 ((number of live pups  on nursing day 4/number of live pups on nursing day 0) x 100) were  calculated. Dead pups were autopsied and abnormality and internal organs  were observed

Postmortem examinations (parental animals):

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
-Macroscopic: organ weights: testes and epididymides; females, ovaries and uteri were extracted, the pregnancy corpora lutea number of the ovary was counted under the stereoscopic microscope, the implantation number of the uterus was counted, and the implantation rate ((implantation number/pregnancy corpora lutea number) x 100) was calculated.
-Microscopic: 5 animals/sex/control and high dose group- sperm and prostrate ventral lobes of all males and vagina, ovaries and uteri of all females; also testes, epididymides, ovaries found to be abnormal during pathologic examinations were all examined histopathologically.

Postmortem examinations (offspring):

no details given

Statistics:

Fisher's Exact Test- mating and conception rate,  Mann-Whitney U Test (2-tailed) and Fisher's Exact Test (1-tailed)-  histopathological examinations, Dunnett's Multiple Comparison Test  (significance level=5%)- body weight, food consumption, hematology,  clinical chemistry and organ weights

Reproductive indices:

-Copulation: When mating was confirmed that day was reckoned as pregnancy  day 0.  From the results of copulation, mating rate ((number of animals  mated/number of animals cohabited) x 100), conception rate ((number of  animals conceived/number of animals mated) x 100), number of days needed  for mating from the start of cohabitation and the number of times of  estrus which recurred during that time were calculated.

-Observation of delivery: With all cases where delivery was confirmed,  the pregnancy period (number of days from pregnancy day 0 to delivery  day) was calculated and the birth rate ((number of females who delivered  live pups/number of animals conceived) x 100) for each group was found. 

Offspring viability indices:

-Number of delivered pups:  The number of delivered pups (live pups +  stillborns) was counted on nursing day 0, and the delivery rate ((number  of delivered pups/number of implantation traces) x 100) and the live  birth rate ((number of delivered live pups/number of implantation traces)  x 100) were calculated. With the delivered pups, external malformation  and the sex were checked and the sex ratio ((number of male live  pups/number of female live pups) x 100) was calculated.
-Number of dead pups: The number of dead pups was checked daily, and the  birth rate ((number of delivered live pups/number of delivered pups) x  100) and the viable rate of new-born pups on day 4 ((number of live pups  on nursing day 4/number of live pups on nursing day 0) x 100) were  calculated. Dead pups were autopsied and abnormality and internal organs  were observed

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not specified

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

-Mortality and time to death: 1 male given 200 mg/kg/day died on day 25, 1 male given 200 mg/kg/day died on day 42 and 1 female died on pregnancy day 22 (administration day 38)
-Clinical signs prior to death (200 mg/kg/day): Day 25 male, showed salivation, emaciation, abnormal breathing noise and dyspnea from administration day 19, and vulval periphery fur soil and loose passage were observed from the day before the death. Day 42 male, showed salivation, emaciation, abnormal breathing noise, dyspnea, a drop in body temperature, faded auricle, tottering and brown soil around the nose were observed from administration day 10, although discontinuously. The female was observed with salivation and abnormal breathing noise sporadically from administration day 11.
-Clinical signs in surviving animals: 200 mg/kg/day: Males- salivation 10/13, abnormal breathing noise 3/13, and decreased contact response 1/13; Females-salivation 10/13, abnormal breathing noise 3/13, and emaciation 1/13. 40 mg/kg/day: no abnormalities
-Body weights: Males- No significant differences in body weights at 200 mg/kg/day; however, body weight gains were decreased when compared to controls. There were no significant differences in body weight or body weight gains in males administered 40 mg/kg/day. Females- No significant differences in body weight or body weight gains.
There was no effect of trimethylamine administration on body weights and food consumption of the females and on organ weights, urine examination and hematological examination results in the males and females
-Clinical chemistry: Significant increase in urea nitrogen at  40  mg/kg/day

Dose descriptor:

NOAEL

Remarks:

systemic effects

Effect level:

40 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Systemic toxicity was observed at 200 mg/kg bw

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

200 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: no effects

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

systemic toxicity at 200 mg/kg bw

Mortality / viability:

no mortality observed

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:

no effects observed

Histopathological findings:

not specified

There were no effects on the viability of the delivered pups, sex ratio, body weight and gross development.

Dose descriptor:

NOAEL

Remarks:

offspring

Generation:

F1

Effect level:

200 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: no effects on the viability of the delivered pups, sex ratio, body weight and gross development

Reproductive effects observed:

not specified

Conclusions:

Daily oral administration of trimethylamine by gavage resulted in the death of two males and 1 female administered 200 mg/kg/day. Abnormal breathing noise, salivation immediately after the administration, ulcers and inflammatory changes in the stomach and intestinal tracts, squamous hyperplasia and edema in submucosa were observed in both males and females in the 200 mg/kg/day group. An inhibition tendency in body weight increase, decrease in food consumption, total protein concentration and albumin concentration were also observed in the males in the same group.

There was no effect of trimethylamine administration on body weights and food consumption of the females and on organ weights, urine examination and hematological examination results in the males and females. Therefore it was inferred that the general toxicological NOAEL (No Observed Adverse Effect Level) is 40 mg/kg/day.

Executive summary:

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed in accordance with OECD guideline 422 (Takashima et al., 2003). Male and female rats (Sprague-Dawley, 13 animals/sex/dose group) were exposed to a daily oral (gavage) administration of trimethylamine at 0, 8, 40, and 200 mg/kg/day during 42 day. Males were exposed for 28 days (2 weeks prior breeding and 2 weeks through breeding). Females were exposed 2 weeks prior breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).

Each one male given 200 mg/kg/day died on administration day 25, 38, and 42 respectively. Day 25 male, showed salivation, emaciation, abnormal breathing noise and dyspnoea from administration day 19, and vulval periphery fur soil and loose passage were observed from the day before the death. Day 42 male, showed salivation, emaciation, abnormal breathing noise, dyspnoea, a drop in body temperature, faded auricle, tottering and brown soil around the nose were observed from administration day 10, although discontinuously. The female was observed with salivation and abnormal breathing noise sporadically from administration day 11.

Clinical signs in surviving animals: 200 mg/kg/day: Males- salivation 10/13, abnormal breathing noise 3/13, and decreased contact response 1/13; Females-salivation 10/13, abnormal breathing noise 3/13, and emaciation 1/13. 40 mg/kg/day: no abnormalities -Body weights: Males- No significant differences in body weights at 200 mg/kg/day; however, body weight gains were decreased when compared to controls. There were no significant differences in body weight or body weight gains in males administered 40 mg/kg/day. Females- No significant differences in body weight or body weight gains. There was no effect of trimethylamine administration on body weights and food consumption of the females and on organ weights, urine examination and hematological examination results in the males and females.There was a significant increase in urea nitrogen at 40 mg/kg/day.

Maternal toxicity did not occur at 200 mg/kg, and no embryo-/fetotoxicity was observed. No abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of estrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, and nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and gross development. From the above, it was considered that reproductive/developmental toxicity NOEL is 200 mg/kg/day for both males and females and also for delivered pups. The parental systemic toxicity is 40 mg/kg bw.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

good quality

Additional information

To assess toxicity of tripropylamine to reproduction read-across of data on closely related substances TMA and TBA was conducted.

Combined repeat dose and reproductive/developmental toxicity screening test (trimethylamine, CAS No. 75 -50 -3)

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed in accordance with OECD guideline 422 (Takashima et al., 2003). Male and female rats (Sprague-Dawley, 13 animals/sex/dose group) were exposed to a daily oral (gavage) administration of trimethylamine at 0, 8, 40, and 200 mg/kg/day during 42 day. Males were exposed for 28 days (2 weeks prior breeding and 2 weeks through breeding). Females were exposed 2 weeks prior breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).

Systemic effects were noted in treated animals at the highest dose tested. Each one male given 200 mg/kg/day died on administration day 25, 38, and 42 respectively. Day 25 male, showed salivation, emaciation, abnormal breathing noise and dyspnoea from administration day 19, and vulval periphery fur soil and loose passage were observed from the day before the death. Day 42 male, showed salivation, emaciation, abnormal breathing noise, dyspnoea, a drop in body temperature, faded auricle, tottering and brown soil around the nose were observed from administration day 10, although discontinuously. The female was observed with salivation and abnormal breathing noise sporadically from administration day 11. Clinical signs in surviving animals were following: males in 200 mg/kg bw group showed salivation (10/13), abnormal breathing noise (3/13), and decreased contact response (1/13); females showed salivation (10/13), abnormal breathing noise (3/13), and emaciation (1/13). In the surviving 40 mg/kg/day dosing group no abnormalities in clinical signs were notes. There were no significant differences in body weights of males at 200 mg/kg/day; however, body weight gains were decreased when compared to controls. There were no significant differences in body weight or body weight gains in males administered 40 mg/kg/day. No significant differences in body weight or body weight gains in females were noted at the highest and mid doses groups. There was no effect of trimethylamine administration on food consumption of the females and on organ weights, urine examination and hematological examination results in the males and females.There was a significant increase in urea nitrogen at 40 mg/kg/day.

Maternal toxicity did not occur at 200 mg/kg, and no embryo-/foetotoxicity was observed. No abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of oestrous cycle was found. There were no effects on the mating rate, conception rate, the birth rate, pregnancy period, lactation state, the number of corpora lutea and the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and gross development. Due to systemic toxicity observed at 200 mg/kg bw, the parental NOAEL for systemic toxicity was 40 mg/kg bw/day. The reproductive toxicity fertility NOAEL is 200 mg/kg/day for both males and females and also for delivered pups.

Prenatal developmental study (tributylamine, CAS No. 102 -82 -9)

Pregnant Sprague-Dawley rats (20 per group) were orally treated (purity of test item: 99.3%) by gavage on gestation days 6 -15 with doses of 15, 45 and 135 mg/kg/day (Mitterer, 1991; Report No. 6031/90). Maternal effects were observed only in the highest dose group. Three dams died prematurely on days 7 and 8. These animals showed red discoloration of the lungs. The other animals of this group showed transient reductions in food consumption and body weight gain. The LOAEL for maternal toxicity was 135 mg/kg bw/day, the NOAEL 45 mg/kg bw/day.

Short description of key information:
No reproductive adverse effects were observed at dose levels which produced parental systemic toxicity in treated animals (TMA and TBA). The MAK value of 1 ppm is proposed as the appropriate value to ensure that adverse reproductive effects do not occur.

Justification for selection of Effect on fertility via oral route:
TMA is a structurally related substance to tripropylamine (both are tertiary amines)

Effects on developmental toxicity

Description of key information

The closely related substances TMA and TBA were not embyro- or foetotoxic and induced no malformations in rats at doses which produced parental toxicity. NOAEL for developmental effects was the highest dose level tested in both studies. The MAK value of 1 ppm is considered to be sufficient for controlling risk of developmental toxicity.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No data on detailed clinical observation,  sensory reactivity to stimuli, assessment of grip strength, and motor  activity.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD 422/OPPTS 870.3650 - Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test

Deviations:

yes

Remarks:

No data on detailed clinical observation,  sensory reactivity to stimuli, assessment of grip strength, and motor activity.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

no details given

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

water

Details on exposure:

no details given

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no details given

Details on mating procedure:

Male/female per cage maximum for 2 weeks beginning  evening of dosing day 15.  Mating confirmed by existence of sperm in the vaginal plug and vaginal smear every morning.

Duration of treatment / exposure:

42 days; Females: 2 weeks prior to breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).

Frequency of treatment:

Once daily

Duration of test:

day 40 or 54

Remarks:

Doses / Concentrations:
0, 8, 40, 200 mg/kg/day (in water)
Basis:

No. of animals per sex per dose:

13/sex/dose group

Control animals:

yes, concurrent vehicle

Details on study design:

Sex: male/female
Duration of test: None

Maternal examinations:

-Clinical Observations and Frequency: General condition was observed at  least once a day during mating and at least twice a day before and after dosing over the administration period.  The state of delivery was recorded.  The state of nursing was observed daily after delivery. 

-Body weights: Parent: Body weights for males were determined on days 1,  7, 14, 21, 28, 35, 42 and on the day of necropsy.  Body weights were  determined for all females on days 1, 7, 14.  Females who took time before mating were weighed on days 35 and 42.  Females who copulated were weighed on pregnancy days 0, 7, 14 and 20.  Females who delivered were  weighed on nursing days 0, 4, and on the day of necropsy.  Females who  copulated but did not deliver were weighed on the equivalent of pregnancy  day 25 (day of necropsy).  

-Observation of delivery: With all cases where delivery was confirmed,  the pregnancy period (number of days from pregnancy day 0 to delivery day) was calculated and the birth rate ((number of females who delivered  live pups/number of animals conceived) x 100) for each group was found. 

Ovaries and uterine content:

Ovaries and  uteri were extracted, the pregnancy corpora lutea number of the ovary was counted under the stereoscopic microscope, the implantation number of the  uterus was counted, and the implantation rate ((implantation  number/pregnancy corpora lutea number) x 100) was calculated.

Fetal examinations:

Fetus: Pup weight was recorded on day 0 and 4  of lactation.
With the delivered pups, external malformation and the sex were checked and the sex ratio ((number of male live pups/number of female live pups) x 100) was calculated.
-Number of dead pups: The number of dead pups was checked daily, and the birth rate ((number of delivered live pups/number of delivered pups) x 100) and the viable rate of new-born pups on day 4 ((number of live pups on nursing day 4/number of live pups on nursing day 0) x 100) were calculated. Dead pups were autopsied and abnormality and internal organs were observed
-Number of delivered pups:  The number of delivered pups (live pups +  stillborns) was counted on nursing day 0, and the delivery rate ((number  of delivered pups/number of implantation traces) x 100) and the live  birth rate ((number of delivered live pups/number of implantation traces)  x 100) were calculated. With the delivered pups, external malformation  and the sex were checked and the sex ratio ((number of male live  pups/number of female live pups) x 100) was calculated.
-Macroscopic: pups were autopsied on day 4  and external and internal organs observed; 

Statistics:

Fisher's Exact Test- mating and conception rate

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
-Mortality and time to death: 1 female died on pregnancy day 22  (administration day 38)
-Clinical signs prior to death (200 mg/kg/day): The female was observed  with salivation and abnormal breathing noise sporadically from administration day 11.

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

As a result of pathological examinations, no abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of estrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and form. From the above, it was considered that reproductive/developmental toxicity NOEL is 200 mg/kg/day for both males and females and also for delivered pups.

Conclusions:

The NOAEL of 200 mg/kg bw, the highest dose level tested, was established for reproductive and developmental toxicity.

Executive summary:

According to OECD guideline 422 rats (Sprague-Dawley) were investigated for developmental toxicity by oral adminstration (gavage) with trimethylamine. The test duration was 42 days, the dosis was given once per day. The concentrations were 0, 8, 40, 200 mg/kg/day (in water). As a result of pathological examinations, no abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of estrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and form. From the above, it was considered that reproductive/developmental toxicity NOEL is 200 mg/kg/day for both males and females and also for delivered pups.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

good quality

Additional information

To assess developmental toxicity of tripropylamine read-across of data from closely related substances TMA and TBA was conducted.

Combined repeat dose and reproductive/developmental toxicity screening test (trimethylamine, CAS No. 75 -50 -3)

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed in accordance with OECD guideline 422 (Takashima et al., 2003). Male and female rats (Sprague-Dawley, 13 animals/sex/dose group) were exposed to a daily oral (gavage) administration of trimethylamine at 0, 8, 40, and 200 mg/kg/day during 42 day. Males were exposed for 28 days (2 weeks prior breeding and 2 weeks through breeding). Females were exposed 2 weeks prior breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).

Due to systemic toxicity observed at 200 mg/kg bw, the parental NOAEL for systemic toxicity was 40 mg/kg bw/day (please see above). There were no effects on the viability of the delivered pups, sex ratio, body weight and gross development. The developmental toxicity NOAEL is 200 mg/kg bw/day.

Prenatal developmental study (tributylamine, CAS No. 102 -82 -9)

Pregnant Sprague Dawley rats (20 per group) were orally treated (purity of test item 99.3%) by gavage on gestation days 6 -15 with dose 15, 45 and 135 mg/kg bw/day (Mitterer, 1991; Report No. 6031/90). In the highest dose group, three dams died prematurely on days 7 and 8. The other animals of this group showed transient reduction in food consumption and body weight gain. There were no embryo- or foetotoxic effects except a slight and dose-related increase in foetal body weight gain, which was significant at the highest dose. The treatment did not produce malformation. The LOAEL for maternal toxicity was 135 mg/kg bw/day and the NOAEL for maternal toxicity was 45 mg/kg bw/day. The NOAEL for developmental toxicity was 135 mg/kg bw/day, the highest dose tested.

Justification for selection of Effect on developmental toxicity: via oral route:
TMA is a structurally related substance to tripropylamine (both are tertiary amines).

Justification for classification or non-classification

There is conclusive but insufficient data for classification of the test substance with regard to fertility and developmental effects. Structurally related amines did not induce reproductive toxicity and developmental malformations in treated animals up to the highest dose level tested. Based on these data, tripropylamine does not need to be classified for this endpoint in accordance with CLP Regulation (EC) No 1272/2008.