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EC number: 204-289-6 | CAS number: 118-96-7
Toxicity to reproduction
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
- Deviations:
- yes
- Remarks:
- The test parameters: 19-25°C, relative humidity 30-70%. During the experiment: lowest temp. 18.70°C; highest 25.10°C; highest humidity 71%. These were short-term deviations and did not affect the course of the study or the reliability of the results.
Test material
- Test material form:
- solid: flakes
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: feed
Results and discussion
Results: P0 (first parental generation)
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 75 mg/kg diet
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: 4,50 mg TNT/kg body weight/24h – average dose for mothers in pregnancy period
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- reproductive function (sperm measures)
- Remarks on result:
- other: 15,73 mg TNT/kg of feed/24h in case of parental generation and 26,94 mg TNT/kg body weight/24h in case of second generation F1
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: 15,73 mg TNT/kg body weight/24h – males; 22,94 mg TNT/kg body weight/24h – females
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- food consumption and compound intake
- Remarks on result:
- other: 15,73 mg TNT/kg body weight/24h
- Dose descriptor:
- NOAEL
- Effect level:
- < 75 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- haematology
Results: F1 generation
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Generation:
- F1 (cohort 1A)
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: 26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h - females
- Dose descriptor:
- NOAEL
- Generation:
- F1 (cohort 1B)
- Effect level:
- < 75 mg/kg diet
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: <7,14 mg TNT/kg body weight/24h
- Dose descriptor:
- NOAEL
- Generation:
- F1 (cohort 2A)
- Effect level:
- < 75 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: 7,72 mg TNT/kg body weight/24h – males; 7,14 mg TNT/kg body weight /24 h – females
- Dose descriptor:
- NOAEL
- Generation:
- F1 (cohort 2B)
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: 26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h – females
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
NOAEL and LOAEL values were defined for parameters:
- Amount of feed consumed by parental generation in male group:
NOAEL – 300 mg TNT/kg of feed (15,73 mg TNT/kg body weight/24h)
LOAEL – 1200 mg TNT/kg of feed (70,09 mg TNT/kg body weight/24h).
- Body weight of parental generation animals in female and male group:
NOAEL – 300 mg TNT/kg of feed (15,73 mg TNT/kg body weight/24h – males; 22,94 mg TNT/kg body weight/24h – females)
LOAEL – 1200 mg TNT/kg of feed (70,09 mg TNT/kg body weight/24h – males; 81,96 mg TNT/kg body weight/24h – females).
- Body weight of F generation, cohort 1A in female and male group:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h - females)
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h – males; 101,85 mg TNT/kg body weight/24 h - females).
- Body weight of F generation, cohort 1B in females and male group:
NOAEL < 75 mg TNT/kg of feed (<7,14 mg TNT/kg body weight/24h)
LOAEL < 75 mg TNT/kg of feed (7,14 mg TNT/kg body weight/24h) in case of females
NOAEL – 75 mg TNT/kg of feed (7,72 mg TNT/kg body weight/24h)
LOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h) in case of males.
- Body weight of F generation, cohort 2A in female and male group:
NOAEL, LOAEL < 75 mg TNT/kg of feed (7,72 mg TNT/kg body weight/24h – males; 7,14 mg TNT/kg body weight /24 h – females).
- Body weight of F generation, cohort 2B in female and male group:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h – females).
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h – males; 101,85 mg TNT/kg body weight/24 h – females.
- Birth weight of the offspring:
NOAEL – 75 mg TNT/kg of feed (4,50 mg TNT/kg body weight/24h – average dose for mothers in pregnancy period) in case of females
LOAEL – 300 mg TNT/kg of feed (16,33 mg TNT/kg body weight/24h – average dose for mothers in pregnancy period) in case of females
NOAEL – 300 mg TNT/kg of feed (16,33 mg TNT/kg body weight/24h – average dose for mothers in pregnancy period) in case of males mothers in pregnancy period) in case of females
LOAEL – 1200 mg TNT/kg of feed (61,20 mg TNT/kg body weight/24h – average dose for mothers in pregnancy period) in case of males.
- Sperm parameters – decrease in properly motile spermatozoa (live) number in the parental and F1 generation:
NOAEL – 300 mg TNT/kg of feed (15,73 mg TNT/kg of feed/24h in case of parental generation and 26,94 mg TNT/kg body weight/24h in case of second generation F1)
LOAEL – 1200 mg TNT/kg of feed (70,09 mg TNT/kg of feed/24h in case of parental generation and 105,63 mg TNT/kg body weight/24h in case of second generation F1).
- Forelimb grip strength:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h – females)
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h – males; 101,85 mg TNT/kg body weight/24 h – females).
- Number of erythrocytes, females and males parental generation:
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg TNT/kg body weight/24h – males; <6,74 mg TNT/kg body weight/24h – females).
- Number of erythrocytes, females and males F1 generation, cohort 1A:
NOAEL – 75 mg TNT/kg of feed (7,14 mg TNT/kg body weight/24h) in case of females
LOAEL – 300 mg TNT/kg of feed (26,15 mg TNT/kg body weight/24h) in case of females
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h) in case of males
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h) in case of males.
- Haemoglobin concentration, females and males parental generation:
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg TNT/kg body weight/24h – males; <6,74 mg TNT/kg body weight/24h – females).
- Haemoglobin concentration, females and males cohort 1A, F1 generation:
NOAEL – 300 mg TNT/kg of feed (26,15 mg TNT/kg body weight/24h) in case of females
LOAEL – 1200 mg TNT/kg of feed (101,85 mg TNT/kg body weight in case of females
NOAEL – 75 mg TNT/kg of feed (7,72 mg TNT/kg body weight/24h) in case of males
LOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight) in case of males.
- Haematocrit, males and females parental generation:
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg TNT/kg body weight/24h – males; <12,15 mg TNT/kg body weight/24h – females).
- Haematocrit, females and males cohort 1A, F1 generation:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h)
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h) in case of males – no dose dependence for females.
- Average haemoglobin concentration in erythrocytes (MCHC) in case of F1 generation males:
NOAEL – 75 mg TNT/kg of feed (7,72 mg TNT/kg body weight/24h)
LOAEL – 300 mg TNT/kg of feed (26,94 mg/kg body weight).
- Number of granulocytes (decrease):
NOAEL – 75 mg TNT/kg of feed (4,51 mg TNT/kg body weight/24h) in case of males of parental generation
LOAEL – 300 mg TNT/kg of feed (15,73 mg TNT/kg body weight/24h) in case of males of parental generation
NOAEL – 300 mg TNT/kg of feed (26,15 mg TNT/kg body weight/24h) in case of females of F1 generation, cohort 1A
LOAEL – 1200 mg TNT/kg of feed (101,85 mg TNT/kg body weight/24h) in case of females of F1 generation, cohort 1A.
- Number of granulocytes with segmented nuclei (decrease):
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg/kg body weight /24h) in case of males of parental generation
NOAEL – 300 mg TNT/kg of feed (26,15 mg TNT/kg body weight/24h) in case of females of F1 generation, cohort 1A
LOAEL – 1200 mg TNT/kg of feed (101,85 mg/kg body weight /24h) in case of females of F1 generation, cohort 1A.
- Activated partial thromboplastin time (APTT) parental generation:
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg TNT/kg body weight/24h – males; <6,74 mg TNT/kg body weight/24h – females).
- Alanine aminotransferase (activity decrease) in case of females of parental generation:
NOAEL – 75 mg TNT/kg of feed (6,74 mg TNT/kg body weight/24h)
LOAEL – 300 mg TNT/kg of feed (22,94 mg TNT/kg body weight/24h).
- Aspartic aminotransferase (activity decrease) for cohort 1A males and females of F1 generation:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h – males; 26,15 mg TNT/kg body weight/24 h – females)
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h – males; 101,85 mg TNT/kg body weight/24 h – females).
- Globulins (concentration decrease) in F1 generation males, cohort 1A:
NOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h)
LOAEL – 1200 mg TNT/kg of feed (105,63 mg TNT/kg body weight/24h).
- Cholesterol (concentration decrease) in parental generation males:
NOAEL, LOAEL < 75 mg TNT/kg of feed (<4,51 mg TNT/kg body weight/24h)
- Creatinine (concentration decrease) in F1 generation males, cohort 1A:
NOAEL – 75 mg TNT/kg of feed (7,72 mg TNT/kg body weight/24h)
LOAEL – 300 mg TNT/kg of feed (26,94 mg TNT/kg body weight/24h).
- Sodium – concentration of sodium decrease: NOAEL – 75 mg TNT/kg feed – females F1 generation, cohort 1A:
NOAEL – 75 mg TNT/kg of feed (7,14 mg TNT/kg body weight/24h)
LOAEL – 300 mg TNT/kg of feed (26,15 mg TNT/kg body weight/24h).
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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