L-tryptophan

Carcinogenicity

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975 - 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication/study report which meets basic scientific principles

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 451 (Carcinogenicity Studies)

Deviations:

yes

Remarks:

dosing only for 78 weeks, limited number of animals per group, some parameters such as haematology, clinical chemistry and urinalysis not examined

GLP compliance:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River, Wilmington
Weight (g): ca. 70 – 90
Age (days): 30
Diet: ad libitum
Water: ad libitum
Pre-dose acclimatisation period: 12 d

Environmental conditions:
Temperature (°C): 22 ± 2
Relative humidity (%): 50 ± 10
Photoperiod (hrs dark / hrs light): 9 / 15
Air changes (per hr): 15

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

Test diets were prepared every 2 weeks by mixing a known amount of sifted L-tryptophan with a small amount of Wayne Lab Blox animal meal in a portable mixer, then adding this mixture to the required amount of animal meal and mixing in a twin-shell blender for 10 minutes.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

78 weeks

Frequency of treatment:

continuously via diet on 5 days per week

Post exposure period:

26-27 weeks

Remarks:

Doses / Concentrations:
0, 25000 or 50000 ppm (ca. 0, 1250 or 2500 mg/kg bw/d)
Basis:
nominal in diet

No. of animals per sex per dose:

35 animals/sex/dose and 15 animals/sex as controls

Control animals:

yes, plain diet

Details on study design:

Dose selection rationale: based on a range-finding study

Positive control:

no

Observations and examinations performed and frequency:

CLINICAL / CAGE SIDE OBSERVATIONS: yes (twice daily; palpations of the animals were carried out at each weighing)
BODY WEIGHT: yes (on day 0, thereafter every 2 weeks through week 86 and once every month until termination)

Sacrifice and pathology:

Gross and microscopic examination of major tissues, major organs, and all gross lesions from killed animals and from animals found dead. The following tissues were examined microscopically: skin, muscle, lungs and bronchi, trachea, bone marrow, spleen, lymph nodes, thymus, heart, salivary gland, liver, gallbladder, pancreas, oesophagus, stomach, small intestine, large intestine, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, mammary gland, prostate or uterus, testis or ovary, brain, and sensory organs. Peripheral blood smears were prepared from each animal whenever possible. Occasionally, additional tissues were also examined microscopically. The different tissues were preserved in 10% buffered formalin, embedded in paraffin, sectioned, and stained with haematoxylin and eosin. Special staining techniques were utilized when indicated for more definitive diagnosis.
A few tissues from some animals were not examined, particularly from those animals that died early. Also, some animals were missing, cannibalized, or judged to be in such an advanced state of autolysis as to preclude histopathological evaluation. Thus, the number of animals from which particular organs or tissues were examined microscopically varies, and does not necessarily represent the number of animals that were placed on study in each group.

Other examinations:

no

Statistics:

yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

: differences in mean body weights among dosed and control groups were minimal (statistics not given)

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not specified

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Dose descriptor:

NOAEL

Effect level:

ca. 2 500 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

A bioassay of L-tryptophan for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats. Groups of 35 rats of each sex were administered L-tryptophan at dose levels of 0, 25000 or 50000 ppm (ca. 0, 1250 or 2500 mg/kg bw/d) on 5 days per week for 78 weeks, and then observed for 26 or 27 weeks. Matched controls consisted of groups of 15 rats of each sex. All surviving rats were killed at 104 or 105 weeks. L-tryptophan had little toxic effect on the rats, as mean body weight loss was minimal and survival of dosed groups of both sexes was high. Sufficient numbers of rats were at risk to termination of the study for development of late-appearing tumours. No neoplasms occurred in a statistically significant incidence among dosed rats when compared to controls. It can be concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 500 mg/kg bw/day

Study duration:

chronic

Species:

rat

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

L-tryptophan was not carcinogenic in rats and mice under the conditions of the NCI study. No classification according to EU and GHS criteria is necassary.

Additional information

A bioassay of L-tryptophan for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats. Groups of 35 rats of each sex were administered L-tryptophan at dose levels of 0, 25000 or 50000 ppm (ca. 0, 1250 or 2500 mg/kg bw/d) on 5 days per week for 78 weeks, and then observed for 26 or 27 weeks. Matched controls consisted of groups of 15 rats of each sex. All surviving rats were killed at 104 or 105 weeks. L-tryptophan had little toxic effect on the rats, as mean body weight loss was minimal and survival of dosed groups of both sexes was high. Sufficient numbers of rats were at risk to termination of the study for development of late-appearing tumours. No neoplasms occurred in a statistically significant incidence among dosed rats when compared to controls. It can be concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats.

In a parallel study, groups of 35 B6C3F1 mice of each sex were dosed with 0, 25000 or 50000 ppm (ca. 0, 3750 or 7500 mg/kg bw/d) on 5 days per week for 78 weeks, and then observed for 26 weeks. Matched controls consisted of groups of 15 mice of each sex. All surviving mice were killed at 104 weeks. In both male and female mice, neoplasms of the hematopoietic system occurred at higher incidences in the low-dose groups than in the matched-control groups (males: controls 0/12, low-dose 9/34, high-dose 2/33; females: controls 2/13, low-dose 6/33, high-dose 1/35). These incidences, however, are not statistically significant and therefore, no tumors are considered to be related to the administration of the test chemical. It can be concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for B6C3F1 mice.