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EC number: 201-494-2 | CAS number: 83-67-0
- 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
Description of key information
Weight of evidence: Two studies are available and can be used in a weight of evidence. Few doses were tested, few examinations were performed and they did not correctly follow a internationally accepted guideline. However, theobromine effects in the testes were identified in both studies.
Link to relevant study records
- Endpoint:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 20 April 1982- 27 September 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- Test method according reproductive assessment by continuous breeding (NTP). GLP study. General lack of information on method.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Qualifier:
- according to guideline
- Guideline:
- other: National Toxicology Program U.S. Reproductive Assessment by Continuous Breeding
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: CD-1 (ICR)BR outbred albino
- Sex:
- male/female
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 120 days mininum.
- Frequency of treatment:
- Daily with feed.
- Dose / conc.:
- 126 mg/kg bw/day (nominal)
- Dose / conc.:
- 335 mg/kg bw/day (nominal)
- Dose / conc.:
- 630 mg/kg bw/day (nominal)
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
WATER CONSUMPTION AND COMPOUND INTAKE: Yes
POST-MORTEM EXAMINATIONS: Yes. Organs examined: kidney weight, liver weight
OTHER: Estrous cycle length, absolute testis, epididymis weight, sex accessory gland weight (prostate, seminal vesicle), epidid. sperm parameters (motility, morphology), determination of affected sex (crossover), hormonal analyses (luternizing hormones, follicle stimulating hormones, prolactin, progesteron, estrogen and testosterone. - Sperm parameters (parental animals):
- Parameters examined in all male parental generations: absolute testis, epididymis weight, sex accessory gland weight (prostate, seminal vesicle), epididymis sperm parameters (motility, morphology)
- Litter observations:
- PARAMETERS EXAMINED: The following parameters were examined in F1 and F2 offspring: litters/pair, live pups/litter, pup wt./litter, cumulative days to litter
GROSS EXAMINATION OF DEAD PUPS :no - Postmortem examinations (parental animals):
- SACRIFICEAfter the delivery and analysis of these litters, the first-generation control and high dose animals were killed and necropsied.
- Reproductive indices:
- Reproductive indices were adversely affected by theobromine exposure. The mean number of litters per pair was decreased at the high dose level by 19%.
- Offspring viability indices:
- Live pups per litter dropped by 15% for the low dose, 21% for the medium dose, and 66% for the high dose mice. Additionally, the proportion born alive was reduced by 5 and 35% at the middle and high dose groups, respectively, and pup weight adjusted for litter size was reduced at all dose levels by 4, 13, and 27%, for the low, medium, and high doses.
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- Reproductive toxicity
- Effect level:
- <= 126 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (sperm measures)
- reproductive performance
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- General toxicity
- Effect level:
- < 630 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 630 mg/kg bw/day (nominal)
- System:
- male reproductive system
- Organ:
- testes
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 630 mg/kg bw/day (nominal)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- one control, two middle dose, and one high dose. The variety of postmortem findings and the lack of relationship to dose led to the conclusion that these deaths were not treatment related.
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Dose descriptor:
- NOAEL
- Remarks:
- general toxicity
- Generation:
- F1
- Effect level:
- >= 630 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
- Dose descriptor:
- NOAEL
- Remarks:
- toxicity to reproduction
- Generation:
- F1
- Effect level:
- >= 630 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- Key result
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 126 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to other toxic effects:
- reproductive effects in the absence of other toxic effects
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- The NOAEL for reproductive toxicity was ≤ 0.10% (126 mg/kg bw) and the NOAEL general toxicity was <0.5% (630 mg/kg bw).
- Executive summary:
A Toxicity to Reproduction study was performed with theobromine according to NTP reproductive assessment by continuous breeding method, which is similar to OECD Guideline 416. Data on food and water consumptions, body weights, and clinical signs from the dose-range-finding study were used to set exposure concentrations for the continuous cohabitation phase (126, 335 and 630 mg/kg/day). In the main test, four females died, these deaths were not treatment related. Reproductive indices were adversely affected by theobromine exposure. The mean number of litters per pair was decreased at the high dose level by 19%. Live pups per litter dropped by 15% for the low dose, 21% for the medium dose, and 66% for the high dose mice. Additionally, the proportion born alive was reduced by 5 and 35% at the middle and high dose groups, respectively, and pup weight adjusted for litter size was reduced at all dose levels by 4, 13, and 27%, for the low, medium, and high doses. The mean study day on which each group delivered each litter was increased in all dosed groups. This delay ranged up to 9 days. In the high dose females, significant lengthening was seen even at the first litter. While theobromine consumption did not affect the percent of mice mating or delivering a litter, it clearly reduced female reproductive capability: there was a 74% reduction in the number of live pups delivered of treated females mated to control males, the proportion of those pups born alive was reduced by 50%, and the weight of those pups adjusted for litter size was reduced by 28%. After the delivery and analysis of these litters, the first-generation control and high dose animals were killed and necropsied. While terminal body weights were unchanged, adjusted liver weights increased for both sexes at the high dose by 12% for males and 9% for females. Absolute testis weight decreased by 12% at the high dose. Although epididymal sperm density and motility did not differ between the control and 0.5% theobromine groups, the treated animals had approximately 4-fold more abnormally shaped sperm. At the time of necropsy, blood was taken for hormonal analysis. No differences were seen between the treated and control mice in the parameters checked. In summary, there was evidence that theobromine is a possible a reproductive toxicant (producing fewer live pups per litter and reducing pup weight) at exposure levels that did not affect body weight or mortality, with the female being more sensitive than the male. The NOAEL reproductive toxicity was ≤ 0.10% (126 mg/kg bw) and the NOAEL general toxicity was 0.5 %. (630 mg/kg bw).
Reference
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): no alteration
TEST SUBSTANCE INTAKE (PARENTAL ANIMALS): no alteration
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): Absolute testis weight decreased by 12% at the high dose. Although epididymal sperm density and motility did not differ between the control and 0.5% theobromine groups, the treated animals had approximately 4-fold more abnormally shaped sperm.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): it clearly reduced female reproductive capability: there was a 74% reduction in the number of live pups delivered of treated females mated to control males, the proportion of those pups born alive was reduced by 50%, and the weight of those pups adjusted for litter size was reduced by 28%.
ORGAN WEIGHTS (PARENTAL ANIMALS): adjusted liver weights increased for both sexes at the high dose by 12% for males and 9% for females.
OTHER FINDINGS (PARENTAL ANIMALS). Hormonal analysis: No differences were seen between the treated and control mice in the levels of luternizing hormones, follicle stimulating hormones, prolactin, progesterone, estrogen, and testosterone.
Tables of results. Summary: NTP Reproductive Assessment by Continuous Breeding Study (theobromine):
Dose concentration |
0.10% |
0.25% |
0.5% |
F0 generation |
|||
General toxicity |
Male, female |
Male, female |
Male, female |
Body weight |
No change, No change |
No change, No change |
No change, No change |
Kidney weight |
No observation |
No observation |
No observation |
Liver weight |
No observation |
No observation |
Statistically significant change (p<0.05), Statistically significant change (p<0.05) |
Mortality |
No change, No change |
No change, No change |
No change, No change |
Feed consumption |
No change, No change |
No change, No change |
No change, No change |
Water consumption |
No observation |
No observation |
No observation |
Clinical signs |
No change, No change |
No change, No change |
No change, No change |
Reproductive toxicity |
|||
Litters/pair |
No change |
No change |
Statistically significant change (p<0.05) |
# Live pups/litter; pup wt./litter |
Statistically significant change (p<0.05), Statistically significant change (p<0.05) |
Statistically significant change (p<0.05), Statistically significant change (p<0.05) |
Statistically significant change (p<0.05), Statistically significant change (p<0.05) |
Cumulative days to litter |
Statistically significant change (p<0.05) |
Statistically significant change (p<0.05) |
Statistically significant change (p<0.05) |
Absolute testis, epididymis weight |
No observation |
No observation |
Statistically significant change (p<0.05), No change |
Sex accessory gland weight (prostate, seminal vesicle) |
No observation |
No observation |
No change, No change |
Epidid. sperm parameters (#, motility, morphology) |
No observation |
No observation |
No change, No change, Statistically significant change (p<0.05) |
Estrous cycle length |
No observation |
No observation |
No observation |
Determination of affected sex (crossover) |
Male |
Female |
Both |
Dose level |
No observation |
0.5% |
No observation |
Dose concentration |
No observation |
No observation |
No observation |
F0 generation |
|||
General toxicity |
Male, female |
Male, female |
Male, female |
Body weight |
No observation |
No observation |
No observation |
Kidney weight |
No observation |
No observation |
No observation |
Liver weight |
No observation |
No observation |
No observation |
Mortality |
No observation |
No observation |
No observation |
Feed consumption |
No observation |
No observation |
No observation |
Water consumption |
No observation |
No observation |
No observation |
Clinical signs |
No observation |
No observation |
No observation |
Reproductive toxicity |
|||
Litters/pair |
No observation |
No observation |
No observation |
# Live pups/litter; pup wt./litter |
No observation |
No observation |
No observation |
Cumulative days to litter |
No observation |
No observation |
No observation |
Absolute testis, epididymis weight |
No observation |
No observation |
No observation |
Sex accessory gland weight (prostate, seminal vesicle) |
No observation |
No observation |
No observation |
Epidid. sperm parameters (#, motility, morphology) |
No observation |
No observation |
No observation |
Estrous cycle length |
No observation |
No observation |
No observation |
Summary information |
|
Affected sex? |
Female |
Study confounders: |
None |
NOAEL reproductive toxicity: |
≤ 0.10% |
NOAEL general toxicity: |
< 0.5% |
F1 more sensitive than F0? |
Unclear |
Postnatal toxicity: |
Unknown |
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 126 mg/kg bw/day
- Study duration:
- chronic
- Species:
- mouse
- Quality of whole database:
- The selected study was conducted with a standardized protocol and the test subtance theobromine. The other available study was conducted with coca powder with analytical determination of theobromine.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
WoE
Study 1: A Toxicity to Reproduction study was performed with theobromine according to NTP reproductive assessment by continuous breeding method, which is similar to OECD Guideline 416. Data on food and water consumptions, body weights, and clinical signs from the dose-range-finding study were used to set exposure concentrations for the continuous cohabitation phase (126, 335 and 630 mg/kg/day). Reproductive indices were adversely affected by theobromine exposure. The mean number of litters per pair was decreased at the high dose level by 19%. Live pups per litter dropped by 15% for the low dose, 21% for the medium dose, and 66% for the high dose mice. Additionally, the proportion born alive was reduced by 5 and 35% at the middle and high dose groups, respectively, and pup weight adjusted for litter size was reduced at all dose levels by 4, 13, and 27%, for the low, medium, and high doses. The mean study day on which each group delivered each litter was increased in all dosed groups. This delay ranged up to 9 days. In the high dose females, significant lengthening was seen even at the first litter. While theobromine consumption did not affect the percent of mice mating or delivering a litter, it clearly reduced female reproductive capability: there was a 74% reduction in the number of live pups delivered of treated females mated to control males, the proportion of those pups born alive was reduced by 50%, and the weight of those pups adjusted for litter size was reduced by 28%. After the delivery and analysis of these litters, the first-generation control and high dose animals were killed and necropsied. While terminal body weights were unchanged, adjusted liver weights increased for both sexes at the high dose by 12% for males and 9% for females. Absolute testis weight decreased by 12% at the high dose. Although epididymal sperm density and motility did not differ between the control and 0.5% theobromine groups, the treated animals had approximately 4-fold more abnormally shaped sperm. At the time of necropsy, blood was taken for hormonal analysis. No differences were seen between the treated and control mice in the parameters checked.
In summary, theobromine was found to be a reproductive toxicant (producing fewer live pups per litter and reducing pup weight) at exposure levels that did not affect body weight or mortality, with the female being more sensitive than the male. The NOAEL reproductive toxicity was ≤ 0.10% (126 mg/kg bw) and the NOAEL general toxicity was 0.5 %. (630 mg/kg bw)
Study 2:
A Three-Generation Reproduction Toxicity study was carried with a method similar to OECD Guidelines 416 (two generation).
Male and female Sprague-Dawley rats were continuously exposed to dietary cocoa powder at levels of 0.0, 1.5, 3.5 or 5.0% for three generations. During the initial 12-week growth periods for the F0, F1b and F2b generation rats, mean methylxanthine exposures (mg/kg/day) for males/females were 30/36, 72/86 and 104/126 for the 1.5, 3.5 and 5.0% cocoa powder groups, respectively, No consistent dose-related effects on any of the monitored reproductive indices (mating, fertility, conception, gestation, viability or lactation) were noted over three generations. Minor reductions in mean body weight relative to controls at week 12 were observed in male rats exposed to 3.5 or 5.0% cocoa powder and female rats exposed to 5.0% cocoa powder in the F1b and F2b generations. Renal tubular mineralization in the F0-generation male rats in the 5.0% cocoa powder group was the only statistically elevated histomorphological lesion observed. Plasma cholesterol concentrations in F1b-generation rats were elevated, but cocoa powder did not affect this parameter consistently across multiple generations. Thus, continuous cocoa powder consumption by rats at levels as high as 5.0% (approximately 115 mg /kg-bw/day) of the diet was without effect on reproductive capacity under the conditions of a standard three-generation evaluation.
Short description of key information:
Endpoint selection: Test method according to reproductive assessment by continuous breeding (RACB) protocol (NTP) which is similar to OECD 416. Diverse effects regarding the reproductive performance were found.
The other available study evaluated the reproductive toxicity of cocoa powder, the level of theobromine was determined.
Justification for selection of Effect on fertility via oral route:
The study has a acceptable quality (Klimish score=3) and was conducted with the test subtance theobromine.
Effects on developmental toxicity
Description of key information
Supporting information: Test method according to OECD 414. No data on GLP. A delay in osteogenesis was the only statistically significant finding, nevertheless the authors suggested that these developmental variations should be considered to be biologically insignificant since other conventional signs of embryotoxicity, such as dose-related reductions in foetal weights and frank teratogenicity were absent in this study.
Disregarded developmental toxicity study: A study which examined developmental effects of theobromine was considered disregarded since only two high concentrations of theobromine were used by the intraperitoneal route.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- Supporting study:Only one study is available for the oral route. However the observed effects were present with maternal toxicity. The authors concluded that they should not be regarded as significative.Test method according to OECD 414. No data on GLP. A delay in osteogenesis was observed, however the relevance of such findings is doubtful since other signs of embryotoxicity or frank teratogenicity were absent and the effects were seen with maternal toxicity.Disregarded study: High concentrations, intraperitoneal route.
Additional information
Supporging study: A Prenatal Developmental Toxicity study was carried out according to OECD Guidelines 414. The study was conducted to determine the teratogenic potential of theobromine in rabbits. Theobromine was given either by gavage at dose levels of 0, 25, 75, 125 or 200 mg/kg body weight/day or administered in the diet at 0, 0.0625, 0.125 or 0.1875% (approximately 0, 21, 41 or 63 mg/kg/day, respectively). The duration of exposure was from days 6 to 29 of gestation. Significant maternal mortality (40%) and reduced food consumption were observed at 200mg theobromine/kg/day. Mean foetal weights were similar to those of the control group at 25 or 75 mg theobromine/kg/day, but decreases in foetal body weight and increases in various malformations and developmental variations were observed in groups given 125 or 200 mg/kg/day. Insufficient litters were available for examination in the 200-mg/kg/day dose group because of maternal toxicity/lethality (repetitive exposure by gavage to 200 mg theobromine/kg approached the maternal LD50). No maternal deaths occurred during dietary theobromine exposure. Maternal weight gain and food consumption, and the mean number of corpora lutea were unaffected by the dietary theobromine. Neither foetotoxicity nor teratogenicity was associated with dietary ingestion of theobromine. The foetuses exposed to 0.125% or 0.1875% theobromine had a significantly higher incidence of incompletely ossified or absent sternebrae, indicating a delay in osteogenesis. The predominant compound found in serum after theobromine ingestion was unchanged theobromine, and there was no evidence of bioaccumulation of theobromine in serum during gestation. Based on the delay in osteogenesis of the foetuses exposed to 0.125 and 0.1875 %, the NOAEL for developmental effects would be 0.0625 % in diet which corresponds to 21.24 mg/kg-bw/day, however, the authors suggested that the developmental variations should be considered to be biologically insignificant since other conventional signs of embryotoxicity, such as dose-related reductions in foetal weights and frank teratogenicity were absent in this study.
Justification for selection of Effect on developmental toxicity: via oral route:
No adverse effect observed.
Toxicity to reproduction: other studies
Additional information
Weight of evidence
Study 1: Theobromine was administered by gavage to 4 rats in a concentration of 250 mg/kg for 31 days.The animals were sacrificed on day 32. One testis and epididymis were removed and weighed. The epididymis was saved for the determination of epididymal sperm reserves. The remaining testis was fixed by whole body glutaraldehyde perfusion and processed for morphologic examination. Theobromine caused numerous alterations in the reproductive male tract of the treated rats at a dose level of 250 mg/kg/day.
Study 2: A repeated toxicity study was conducted according to OECD 407, but only the effects on the reproductive organ of the male rats were analyzed. The effects of theobromine on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2 -week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. It was concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.
Justification for classification or non-classification
In a weight of evidence approach the substance theobromine is not classified for reproductive or developmental toxicity in accordance with CLP Regulation (EC) no. 1272/2008.
Additional information
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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